Heterojunction of MXenes and MN4-graphene: Machine learning to accelerate the design of bifunctional oxygen electrocatalysts.

Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are essential for the development of excellent bifunctional electrocatalysts, which are key functions in clean energy production. The emphasis of this study lies in the rapid design and investigation of 153 MN4-graphene (Gra)/ MXene (M2NO) electrocatalysts for ORR/OER catalytic activity using machine learning (ML) and density functional theory (DFT). The DFT results indicated that CoN4-Gra/Ti2NO had both good ORR (0.37 V) and OER (0.30 V) overpotentials, while TiN4-Gra/M2NO and MN4-Gra/Cr2NO had high overpotentials. Our research further indicated orbital spin polarization and d-band centers far from the Fermi energy level, affecting the adsorption energy of oxygen-containing intermediates and thus reducing the catalytic activity. The ML results showed that the gradient boosting regression (GBR) model successfully predicted the overpotentials of the monofunctional catalysts RhN4-Gra/Ti2NO (ORR, 0.39 V) and RuN4-Gra/W2NO (OER, 0.45 V) as well as the overpotentials of the bifunctional catalyst RuN4-Gra/W2NO (ORR, 0.39 V; OER, 0.45 V). The symbolic regression (SR) algorithm was used to construct the overpotential descriptors without environmental variable features to accelerate the catalyst screening and shorten the trial-and-error costs from the source, providing a reliable theoretical basis for the experimental synthesis of MXene heterostructures.

Study of electronic and optical properties of CdI2 modulated by electric field: a first-principles study.

We found that an out-of-plane vertical electric field of 1.0 V/Ang helps to maintain the thermodynamic and kinetic stability of monolayer CdI2.The results indicated that the electric field modulates monolayer CdI2 to produce the Mexican-hat electronic state and the giant Stark effect of the vertical electric field on monolayer CdI2 originates from electric field lifting its conduction band. The results based on HSE06 + SOC calculations show that electric field induces strong spin polarization, leading to significant energy level splitting and spin flipping in the valence band. Based on GW0 + BSE, the electric field broadens effective optical response range of monolayer CdI2, the new peak in the optical absorption spectrum under electric field indicates that electric field helps to diminish excitonic effect of monolayer CdI2.

Establishment and Validation of a Novel Prediction Model for Early Natural Biochemical Recurrence After Radical Prostatectomy Based on Post-Operative PSA at Sixth Week.

Objective: Based on post-operative PSA at 6th week (PSA6w) after radical prostatectomy to establish an optimal model for predicting natural biochemical recurrence (BCR). Methods: A total of 742 patients with post-operative PSA6w from PC-follow database, between January 2003 and October 2022, were included. All the patients had not received any hormone therapy and radiotherapy before operation and BCR. Of these patients, 588 cases operated by one surgeon were enrolled for modelling and another 154 cases operated by other surgeons were for external validation. After screened by Cox regression, the post-operative PSA6w, pathological stage, Gleason Grade and positive surgical margins were adopted for modelling. The R software was used to plot the nomogram of the prediction model for BCR. C-index and calibration curve were calculated to evaluate the new model. Finally, integrated discrimination improvement was adopted to evaluate the prediction performances of the new nomogram model and the classical Kattan nomogram. Results: The C-index of the new model was 0.871 (95% CI: 0.830-0.912). The calibration curve of the new model demonstrated superior consistency between the predicted and actual value. The C-index of the external validation group was 0.850 (95% CI: 0.742-0.958), which demonstrated perfect universality. The integrated discrimination improvement showed a 12.61% improvement in prediction performance over that of the classical Kattan nomogram (P < 0.01). Based on the new nomogram, patients were divided to high and low BCR group with a 3 year BCR-free cutoff probability as 74.72%. Low-risk patients, accounting for 77.89% of the patients, have no need to follow up frequently with a false-negative rate only 5.24%, which will save medical resources to a large extent. Conclusion: Post-operative PSA6w is a sensitive risk biomarker for early natural BCR. The new nomogram model could predict BCR probability with a higher accuracy and will further simplify the clinical follow-up strategies.

Sustainable functional urethral reconstruction improves early urinary continence after robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To evaluate the impact of sustainable functional urethral reconstruction (SFUR) on early recovery of urinary continence (UC) after robot-assisted radical prostatectomy. PATIENTS AND METHODS: Overall, 96 patients with primary prostate cancer were randomised into the SFUR or standard group (n = 48 each). The primary outcome was the 1-month UC recovery. Secondary outcomes included short-term (≤3 months) UC recovery, urinary function, micturition-related bother, perioperative complications, and oncological outcomes. Kaplan-Meier curves and Cox proportional hazard models were used to assess the 3-month UC recovery. Generalised estimating equations were used to compare postoperative urinary function and micturition-related bother. RESULTS: The 1-month UC recovery rates, median 24-h pad weights, and median operative time in the SFUR and standard groups were 73% and 49% (P = 0.017), 0 and 47 g (P = 0.001), and 125 and 103 min (P = 0.025), respectively. The UC recovery rates in the SFUR vs standard groups were 53% vs 23% at 1 week (P = 0.003), 53% vs 32% at 2 weeks (P = 0.038), and 93% vs 77% at 3 months (P = 0.025). The median time to UC recovery in the SFUR and standard groups was 5 and 34 days, respectively (log-rank P = 0.006); multivariable Cox regression supported this result (hazard ratio 1.73, 95% confidence interval 1.08-2.79, P = 0.024). Similar results were observed when UC was defined as 0 pads/day. Urinary function (P = 0.2) and micturition-related bother (P = 0.8) were similar at all follow-up intervals. The perioperative complication rates, positive surgical margin rates, and 1-year biochemical recurrence-free survival were comparable between both groups (all P > 0.05). CONCLUSION: SFUR resulted in earlier UC recovery without compromising postoperative urinary function. Long-term validation and multicentre studies are required to confirm the results of this novel technique.

Transperineal Parallel Biopsy of the Prostate: A New Approach of Tissue Sampling for Precision Medicine.

PURPOSE: Through an observational study to present a new approach for obtaining high-quality samples for the targeted therapy of prostate cancer. PATIENTS AND METHODS: Parallel biopsy, which was defined as collecting the tissue from the same site by two biopsies, was performed on patients with elevated PSA. Each tissue was stained by ink to identify the pathological characteristics, including Gleason score and tumor tissue ratio. Kendall tau-b test and intraclass correlation coefficient test were used to compare the consistency between each paired sample. Then, based on the pathology of the biopsies, high-quality tissues would be selected for sequencing, and PyClone model was used to track the clonal evolution. RESULTS: In total, 252 pairs of biopsies were collected. The consistency of Gleason score between each paired biopsy is 0.777 (p<0.01), and the consistency of tumor tissue ratio is 0.853 (p<0.01). With the application of parallel biopsy, on average five nonsynonymous mutations could be identified in patients with castration-resistant prostate cancer. Six out of eight had at least one biology-relevant alteration in patients, guiding further treatment. Meanwhile, clonal evolution was constructed to investigate the progress of tumor. CONCLUSION: Parallel biopsy is a reliable approach to collect high-quality tissue and shows potential application in precision medicine.

Sustainable functional urethral reconstruction: Maximizing early continence recovery in robotic-assisted radical prostatectomy.

OBJECTIVE: To evaluate the safety profile and short-term functional outcome of sustainable functional urethral reconstruction (SFUR) in robotic-assisted radical prostatectomy (RARP). METHODS: One hundred and sixty-two consecutive prostate cancer patients who underwent RARP were retrospectively analyzed, in which 53 had undergone SFUR while the other 109 had undergone conventional RARP procedures. Immediate, 2-week, 1-month and 3-month continence recovery and other perioperative data were compared to evaluate short-term surgical and functional outcome. RESULTS: The median age was 68 and 67 years in the experimental group and control group, respectively (p=0.206), with a median prostate-specific antigen (PSA) of 13.6 ng/mL (interquartile range [IQR], 8.46-27.32 ng/mL) in the experimental group and 13.84 ng/mL (IQR, 9.12-26.80 ng/mL) in control group (p=0.846). Immediate, 2-week, 1-month and 3-month continence recovery rates between the groups were 34.0% vs. 3.7%, 50.9% vs. 14.7%, 62.3% vs. 27.5%, and 79.2% vs. 63.3% (all p<0.05). The morphological changes made by the new reconstruction technique were maintained on magnetic resonance imaging (MRI) 3 months postoperatively. Nerve-sparing procedures and adoption of the new reconstruction technique were significantly relevant to continence recovery on logistics regression model (p<0.001). CONCLUSIONS: SFUR is a safe and easy-to-handle modification that may contribute to early continence return for RARP. Long-term follow-up and prospective studies are required to further evaluate its value in postoperative quality-of-life improvement.

Short-term therapeutic outcomes of robotic-assisted laparoscopic radical prostatectomy for oligometastatic prostate cancer: a propensity score matching study.

BACKGROUND: The role of local treatment in oligometastatic prostate cancer (PCa) is gaining interest with the oligometastases hypothesis proposed and the improvement of various surgical methods and techniques. This study aimed to compare the short-term therapeutic outcomes of robotic-assisted laparoscopic radical prostatectomy (RALP) for oligometastatic prostate cancer (OPC) vs. localized PCa using propensity score matching. METHODS: Totally 508 consecutive patients underwent RALP as a first-line treatment. The patients were divided into two groups according to oligometastatic state: the OPC group (n = 41) or the localized PCa group (n = 467). Oligometastatic disease was defined as the presence of two or fewer suspicious lesions. The association between the oligometastatic state and therapeutic outcomes of RALP was evaluated, including biochemical recurrence (BCR) and overall survival (OS). A Cox proportional hazards model was used to assess the possible risk factors for BCR. RESULTS: Totally 41 pairs of patients were matched. The median operative time, the median blood loss, the overall positive surgical margin rate, the median post-operative hospital stays, and the post-operative urinary continence recovery rate between the two groups showed no statistical significance. The 4-year BCR survival rates of the OPC group and localized PCa group were 56.7% and 60.8%, respectively, without a significant difference (P = 0.804). The 5-year OS rates were 96.3% and 100%, respectively (P = 0.326). Additionally, the results of Cox regression showed that oligometastatic state was not an independent risk factor for BCR (P = 0.682). CONCLUSIONS: Our findings supported the safety and effectiveness of RALP in OPC. Additionally, oligometastatic state and sites did not have an adverse effect on BCR independently.

Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy-Refractory Testicular Tumors.

Testicular cancer is one of the few tumor types that have not yet benefited from targeted therapy. Still no new active agents for treating this cancer have been identified over the past 15 years. Once patients are refractory to cisplatin-based chemotherapy, they will be expected to die from testicular cancer. This report describes a 21-year-old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low-depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells' progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy-refractory testicular germ cells, CPS regimen may provide a new therapy, but it still warrants further validation in clinical studies. KEY POINTS: Chemotherapy-refractory testicular cancer has a very poor prognosis resulting in a lack of effective targeted therapies. KRAS gene amplification occurs in nearly 20% of testicular cancer and 50% of chemotherapy-refractory testicular cancer. KRAS amplification may activate the MAPK signaling pathway, and inhibition of MAPK by sorafenib combined with paclitaxel and carboplatin could be a viable option based on a phase III clinical trial of melanoma.To the authors' knowledge, this is the first report of response to sorafenib-based combination targeted therapy in a patient with chemotherapy-refractory testicular cancer.Clinical genomic profiling can confirm copy number variation of testicular cancer and provide insights on therapeutic options.

Palliative Transurethral Resection of the Prostate in Patients with Metastatic Prostate Cancer: A Prospective Study of 188 Patients.

Purpose: Palliative transurethral resection of the prostate (pTURP) in metastatic prostate cancer (mPCa) is reported to be rarely applied in clinics. We prospectively evaluated the ability of pTURP to achieve tumor control in patients with mPCa. Patients and Methods: A prospective study of patients with mPCa from 2011 to 2018 was conducted. The patients were divided into two groups: a pTURP + androgen deprivation therapy (ADT) group and an ADT group. Castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival (CSS) were analyzed as research endpoints between the groups using a Kaplan-Meier estimator. Results: A total of 188 patients with mPCa were enrolled in the study from our center, of which 110 patients were in the pTURP + ADT group, and 78 patients were in the ADT group. The basic clinical characteristics were comparable between the groups. There were no reoperations or severe complications in the pTURP + ADT group. The median follow-up was 29 months. The median CRPC-free survival was significantly increased when the 7-month prostate-specific antigen (PSA) was <4 ng/mL (34 vs 6, p < 0.01) and bone metastasis was ≤5 (25 vs 10, p < 0.01) but not in the pTURP + ADT group (16 vs 12, p = 0.267). The 3-year CSS was higher in the pTURP + ADT group than that in the ADT group (95.9% vs 64.9%, p = 0.004), as well as when the 7-month PSA was <4 ng/mL compared to ≥4 ng/mL (90.7% vs 36.6%, p < 0.01) and when bone metastasis was ≤5 compared to >5 (82.2% vs 63.2%, p < 0.01). In subgroup analysis, pTURP + ADT could significantly improve patients' CSS when PSA ≥65 ng/mL, Gleason Score (GS) ≥8, and bone metastasis ≤5. Conclusions: We used our center-based cancer database to analyze survival in patients with mPCa undergoing pTURP. In the study population, pTURP + ADT was indicated to benefit CSS and shown to be safe. Moreover, we suggest that mPCa patients with PSA ≥65 ng/mL, GS ≥8, and bone metastasis ≤5 may perform pTURP before ADT.