Health-related quality of life following salvage radical prostatectomy for recurrent prostate cancer after radiotherapy or focal therapy.

BACKGROUND: Salvage radical prostatectomy (sRP) is an important treatment option for patients with recurrent prostate cancer (PCa) after radiotherapy (RT) or focal therapy (FT). However, health-related quality of life (HRQOL) after sRP depending on the primary treatment is understudied. METHODS: Patients who underwent Salvage RP for recurrent PCa were analyzed. The primary outcome of this study was HRQOL assessed by the quality-of-life questionnaire (QLQ)-C30 and its prostate specific QLQ-PR25 add-on. Secondary outcomes were functional outcome parameters (erectile function, continence) and biochemical recurrence-free survival (BRFS). Statistical analyses employed the chi-square test, Mann-Whitney U test, and Kaplan-Meier method, with a p value < 0.05 denoting significance. RESULTS: 37 patients with RT as primary treatment (RT-sRP) and 22 patients with focal therapy prior sRP (FT-sRP) were analyzed. Mean global health score was not significantly different preoperatively (71.9 vs. 67.3, p = 0.89) as well as after a median of 32 months follow-up (54.9 vs. 50.6, p = 0.63) with impaired HRQOL after sRP in both groups. Baseline erectile dysfunction was more prevalent in the RT-sRP group (mean IIEF-5: 5.0) than in the FT-sRP group (mean IIEF-5: 8.5, p = 0.037). No differences were observed at follow-up for erectile function (IIEF-5-Score: 0.5 vs 2.5, p = 0.199) and continence (continence rate: 48.4% vs 52.9% (p = 0.763) between the RT-sRP and FT-sRP group. 5-year-BRFS was 60% (RT-sRP) and 68% (FT-sRP, p = 0.849). CONCLUSIONS: sRP impacts HRQOL in patients with PCa after RT and FT with no significant differences. Comparison with HRQOL and BRFS of treatment alternatives is paramount to counsel patients for appropriate treatments.

Electro-osmotic flow in nanoconfinement: Solid-state and protein nanopores.

Electro-osmotic flow (EOF) is a phenomenon where fluid motion occurs in porous materials or micro/nano-channels when an external electric field is applied. In the particular example of single-molecule electrophoresis using single nanopores, the role of EOF on the translocation velocity of the analyte molecule through the nanopore is not fully understood. The complexity arises from a combination of effects from hydrodynamics in restricted environments, electrostatics emanating from charge decorations and geometry of the pores. We address this fundamental issue using the Poisson-Nernst-Planck and Navier-Stokes (PNP-NS) equations for cylindrical solid-state nanopores and three representative protein nanopores (α-hemolysin, MspA, and CsgG). We present the velocity profiles inside the nanopores as a function of charge decoration and geometry of the pore and applied electric field. We report several unexpected results: (a) The apparent charges of the protein nanopores are different from their net charge and the surface charge of the whole protein geometry, and the net charge of inner surface is consistent with the apparent charge. (b) The fluid velocity depends non-monotonically on voltage. The three protein nanopores exhibit unique EOF and velocity-voltage relations, which cannot be simply deduced from their net charge. Furthermore, effective point mutations can significantly change both the direction and the magnitude of EOF. The present computational analysis offers an opportunity to further understand the origins of the speed of transport of charged macromolecules in restricted space and to design desirable nanopores for tuning the speed of macromolecules through nanopores.

Metabolic patterns on [18F]FDG PET/CT in patients with unresectable stage III NSCLC undergoing chemoradiotherapy ± durvalumab maintenance treatment.

PURPOSE: In patients with unresectable stage III non-small-cell lung cancer (NSCLC), durvalumab maintenance treatment after chemoradiotherapy (CRT) significantly improves survival. So far, however, metabolic changes of tumoral lesions and secondary lymphoid organs under durvalumab are unknown. Hence, we assessed changes on [18F]FDG PET/CT in comparison to patients undergoing CRT alone. METHODS: Forty-three patients with [18F]FDG PET/CT both before and after standard CRT for unresectable stage III NSCLC were included, in 16/43 patients durvalumab maintenance treatment was initiated (CRT-IO) prior to the second PET/CT. Uptake of tumor sites and secondary lymphoid organs was compared between CRT and CRT-IO. Also, readers were blinded for durvalumab administration and reviewed scans for findings suspicious for immunotherapy-related adverse events (irAE). RESULTS: Initial uptake characteristics were comparable. However, under durvalumab, diverging metabolic patterns were noted: There was a significantly higher reduction of tumoral uptake intensity in CRT-IO compared to CRT, e.g. median decrease of SUVmax -70.0% vs. -24.8%, p = 0.009. In contrast, the spleen uptake increased in CRT-IO while it dropped in CRT (median + 12.5% vs. -4.4%, p = 0.029). Overall survival was significantly longer in CRT-IO compared to CRT with few events (progression/death) noted in CRT-IO. Findings suggestive of irAE were present on PET/CT more often in CRT-IO (12/16) compared to CRT (8/27 patients), p = 0.005. CONCLUSION: Durvalumab maintenance treatment after CRT leads to diverging tumoral metabolic changes, but also increases splenic metabolism and leads to a higher proportion of findings suggestive of irAE compared to patients without durvalumab. Due to significantly prolonged survival with durvalumab, survival analysis will be substantiated in correlation to metabolic changes as soon as more clinical events are present.

Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

Clinical outcomes of conventional HDR intracavitary brachytherapy combined with complementary applicator-guided intensity modulated radiotherapy boost in patients with bulky cervical tumour.

OBJECTIVE: To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). DESIGN: A retrospective cohort study. SETTING: Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, China. POPULATION: Large high-risk clinical target volume (HR-CTV) volume (>40 ml) at the time of brachytherapy cervical cancer patients were recruited. METHODS: This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven-field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR-CTV and IR-CTV were 6 and 5 Gy per fraction for five fractions, respectively. RESULTS: Mean HR-CTV was 65.8 ± 23.6 ml at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7 ± 3.6 Gy and 78.1 ± 2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3 and 56.7 ± 8.7 Gy, respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence-free survival rate, metastasis recurrence-free survival rate, disease-free survival rate and cancer-special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. CONCLUSIONS: The combination of ICBT with an applicator-guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour.

A Pedestrian Detection Network Model Based on Improved YOLOv5.

Advanced object detection methods always face high algorithmic complexity or low accuracy when used in pedestrian target detection for the autonomous driving system. This paper proposes a lightweight pedestrian detection approach called the YOLOv5s-G2 network to address these issues. We apply Ghost and GhostC3 modules in the YOLOv5s-G2 network to minimize computational cost during feature extraction while keeping the network's capability of extracting features intact. The YOLOv5s-G2 network improves feature extraction accuracy by incorporating the Global Attention Mechanism (GAM) module. This application can extract relevant information for pedestrian target identification tasks and suppress irrelevant information, improving the unidentified problem of occluded and small targets by replacing the GIoU loss function used in the bounding box regression with the α-CIoU loss function. The YOLOv5s-G2 network is evaluated on the WiderPerson dataset to ensure its efficacy. Our proposed YOLOv5s-G2 network offers a 1.0% increase in detection accuracy and a 13.2% decrease in Floating Point Operations (FLOPs) compared to the existing YOLOv5s network. As a result, the YOLOv5s-G2 network is preferable for pedestrian identification as it is both more lightweight and more accurate.

Pooled analysis on image-guided moderately hypofractionated thoracic irradiation in inoperable node-positive/recurrent patients with non-small cell lung cancer with poor prognostic factors and severely limited pulmonary function and reserve.

BACKGROUND: The objective of this study was to investigate the feasibility and efficacy of image-guided moderately hypofractionated thoracic radiotherapy (hypo-IGRT) in patients with non-small cell lung cancer (NSCLC) with poor performance status and severely limited pulmonary function and reserve. METHODS: Consecutive inoperable patients who had node-positive, stage IIB-IIIC (TNM, 8th edition) or recurrent NSCLC, had an Eastern Cooperative Oncology Group performance status ≥1, and had a forced expiratory volume in 1 second (FEV1 ) ≤1.0 L, had a single-breath diffusing capacity of the lung for carbon monoxide (DLCO-SB) ≤40% and/or on long-term oxygen therapy were analyzed. All patients received hypofractionated IGRT to a total dose of 42.0 to 49.0 Gy/13 to 16 fractions (2.8-3.5 Gy/fraction) (equivalent dose in 2-Gy fractions/biologically effective dose [α/ß = 10] = 45.5-55.1 Gy/54.6-66.2 Gy) alone. Patients were monitored closely for nonhematological toxicity, which was classified per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Between 2014 and 2021, 47 consecutive patients with a median age of 72 years (range, 52.2-88 years) were treated. At baseline, the median FEV1 , vital capacity, and DLCO-SB were 1.17 L (range, 0.69-2.84 L), 2.34 L (range, 1.23-3.74 L), and 35% predicted (range, 13.3%-69.0%), respectively. The mean and median planning target volumes were 410.8 cc (SD, 267.1 cc) and 315.4 cc (range, 83.4-1174.1 cc). With a median follow-up of 28.9 months (range, 0.5-90.6 months) after RT, the median progression-free survival (PFS)/overall survival (OS) and 6- and 12-month PFS/OS rates were 10.4 months (95% CI, 7-13.8 months)/18.3 months (95% CI, 9.2-27.4 months), 70%/89.4%, and 38.8%/66%, respectively. Treatment was well tolerated with only 1 case each of grade 3 pneumonitis and esophagitis. No toxicity greater than grade 3 was observed. CONCLUSIONS: Patients with inoperable node-positive NSCLC, a poor performance status, and severely limited lung function can be safely and effectively treated with individualized moderately hypofractionated IGRT. The achieved survival rates for this highly multimorbid group of patients were encouraging.

Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.

BACKGROUND: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). METHOD AND PATIENTS: Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local-regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). RESULTS: All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60 Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0-42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7-34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 months, p = 0.020) and eMFS (8.1 months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8 months (p < 0.001) and 3.6 months vs. not reached (p = 0.001), respectively. PTV as a continuous variable also had a significant impact on eMFS (p = 0.048). However, no significant association of different PTV cut-offs or PTV as a continuous variable with LRPFS and BMFS could be shown. The multivariate analysis that was performed for PTV ≥ 900ccm and age (≥ 65 years), gender (male), histology (non-ACC) as well as T- and N-stage (T4, N3) as covariates also revealed PTV ≥ 900ccm as the only factor that had a significant correlation with PFS (HR: 5.383 (95% CI:1.263-22.942, p = 0.023)). CONCLUSION: In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm.

Radiotherapy in oligometastatic prostate cancer-a pattern of care survey among members of the German Society for Radiation Oncology (DEGRO).

PURPOSE: Due to improved imaging, oligometastatic prostate cancer (OMPC) is diagnosed more frequently. Growing evidence shows that patients with a limited number of metastases benefit from primary-directed radiotherapy (PDT) as well as from metastasis-directed radiotherapy (MDT). This survey investigates the current treatment practice for OMPC among German-speaking radiation oncologists. METHODS: Members of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie [DEGRO]) were surveyed regarding their current treatment practice via an anonymous online questionnaire sent by email. The survey included six general items and 14 specific items regarding treatment characteristics. Questionnaires with at least 50% of questions completed were considered for further analysis. RESULTS: A total of 204 responses were received (15% response rate), 167 were considered for further analysis. Most respondents stated to be specialized in treating prostate cancer patients and to treat 10-30 patients with OMPC per annum; 97% considered PSMA-PET/CT necessary to define oligometastatic disease. Opinions differed regarding the use of systemic therapies: 63% of the respondents aimed to defer systemic therapy using radiotherapy in OMPC, whereas 37% considered systemic therapy necessary. In the setting of synchronous OMPC, 97% recommended PDT with or without a combination of MDT and/or systemic therapy. For metachronous nodal or bone oligometastatic recurrence, 98 and 99%, respectively, would opt for MDT. The majority would combine MDT with systemic therapy in patients with metachronous oligorecurrence. Respondents recommended normofractionation, hypofractionation, and SBRT for lymph node metastases in 49, 27, and 24%, respectively. No consensus existed regarding the field size for MDT of lymph node metastases. Most respondents preferred > 5 fractions for treatment of bone metastases. CONCLUSION: Local radiotherapy for PDT and MDT is routinely used among respondents of this survey, representing 12% of all German-speaking radiation oncologists. The timing of systemic therapy, fractionation schedules, and field sizes are handled differently and remain an area of active investigation.

Outcome after PSMA-PET/CT-based salvage radiotherapy for nodal recurrence after radical prostatectomy.

PURPOSE: Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. METHODS: A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method and uni- and multivariate analysis was performed. RESULTS: Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1-40.1) in patients with bcP and 1.4 ng/ml (range 0.3-5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60-70 Gy) was delivered to the prostatic fossa, 70 Gy (66-72 Gy) to the local recurrence, if present, 65.1 Gy (56-66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4-50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. CONCLUSIONS: Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.

Differential role of residual metabolic tumor volume in inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition.

BACKGROUND: The PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI). METHODS: Fifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18F-FDG PET/CT using a standard threshold (liver SUVmean + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS). RESULTS: Overall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses. CONCLUSION: In stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load.

Primary radiation therapy in stage I/II indolent orbital lymphoma - a comprehensive retrospective recurrence and toxicity analysis.

PURPOSE OR OBJECTIVE: To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann-Arbor classification) indolent orbital lymphoma. MATERIAL AND METHODS: We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy-proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose. RESULTS: At diagnosis, the median age was 63.5 years (range: 20-92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty-eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6 Gy (range: 21.6-48.6 Gy) delivered in 1.8-2 Gy single fractions. At a median follow-up of 83 months (range: 7-258 months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5- and 10-year PFS rates were 79.2% (95% CI: 73.0%-85.4%) and 67.6% (95% CI: 59.4%-75.8%); 5- and 10-year OS was 83.6% (95% CI: 77.9%-89.3%) and 76.5% (95% CI: 69.4%-83.6%), respectively. In total, 66 acute toxicity events (all-grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract. CONCLUSION: Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra-low-dose radiotherapy and anti-CD20 monoclonal antibodies to further mitigate long-term sequelae.

WITHDRAWN: lncRNA Linc00173 modulates glucose metabolism and multidrug chemoresistance in SCLC: Potential molecular panel for targeted therapy.

This article has been withdrawn at the request of the editor-in-chief. Following publication of this article, the editor-in-chief discovered evidence of image duplication in Figures 1I, 1J, 3F, S5B, and S6B. Given the duplication of several western blots representing several gene products, the editor-in-chief has lost faith in the findings presented in this article. The authors maintain that these image duplications were the result of errors in file management and do not affect the conclusions of the study. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Salt-Induced Liquid-Liquid Phase Separation: Combined Experimental and Theoretical Investigation of Water-Acetonitrile-Salt Mixtures.

Salt-induced liquid-liquid phase separation in liquid mixtures is a common phenomenon in nature and in various applications, such as in separation and extraction of chemicals. Here, we present results of a systematic investigation of the phase behaviors in water-acetonitrile-salt mixtures using a combination of experiment and theory. We obtain complete ternary phase diagrams for nine representative salts in water-acetonitrile mixtures by cloud point and component analysis. We construct a thermodynamic free energy model by accounting for the nonideal mixing of the liquids, ion hydration, electrostatic interactions, and Born energy. Our theory yields phase diagrams in good agreement with the experimental data. By comparing the contributions due to the electrostatic interaction, Born energy, and hydration, we find that hydration is the main driving force for the liquid-liquid separation and is a major contributor to the specific ion effects. Our theory highlights the important role of entropy in the hydration driving force. We discuss the implications of our findings in the context of salting-out assisted liquid-liquid extraction and make suggestions for selecting salt ions to optimize the separation performance.

Timing of Radiotherapy after Radical Prostatectomy: Effects on Health-Related Quality of Life.

PURPOSE: The optimal timing of radiotherapy (RT) after radical prostatectomy (RP) remains controversial with unknown impact on health-related quality of life (HRQOL). We aimed to compare the influence of early RT (eRT) and deferred RT (dRT) on HRQOL. MATERIALS AND METHODS: A total of 4,511 patients were analyzed. Inclusion criteria encompassed: ≥pT3, International Society of Urological Pathology grade ≥4, or positive surgical margin. A 1:4 propensity score-matched-analysis of 1,599 patients was conducted (307: eRT, ≤6 months after RP; 1,292: dRT, >6 months after RP). Primary end point was general HRQOL (based on European Organisation for Research and Treatment of Cancer QLQ-C30). Pearson correlation and binary logistic regression models were used to estimate the impact of timing of RT on HRQOL. Functional outcome was assessed using the International Consultation on Incontinence Questionnaire, short form (ICIQ-SF) and International Index of Erectile Function (IIEF-5) questionnaires. RESULTS: Median followup was 38 months. At 12 months and 24 months followup, general HRQOL scores were significantly higher for dRT (52.7 vs 35.5; p=0.001; 45.8 vs 37.3; p=0.026). ICIQ-SF scores were higher (8.5 vs 6.1; p=0.001; 8.4 vs 7.3; p=0.038), and IIEF-5 scores were lower (1.8 vs 4.2; p=0.001; 2.2 vs 4.4; p=0.005) for eRT at 12 months and 24 months. On multivariate-analysis, dRT was associated with superior general HRQOL at 12 months (OR 0.59, 95% CI 0.37-0.94, p=0.027) and 24 months (OR 0.64, 95% CI 0.39-0.99, p=0.043), respectively. A longer time interval between RP and RT was associated with improved general HRQOL (OR 1.09, 95% CI 1.038-1.143; p <0.001). CONCLUSIONS: dRT yields improved short-term HRQOL compared to eRT. Since longer time intervals between RP and RT predict better short-term HRQOL, our data provide further support for the concept of deferred RT at low prostate specific antigen recurrence.

Effect of Hydrophobicity and Charge Separation on the Antifouling Properties of Surface-Tethered Zwitterionic Peptides.

Zwitterionic peptides emerge as a class of highly effective antifouling material in a wide range of applications such as biosensors, biomedical devices, and implants. We incorporated neutral amino acid spacers with different hydrophobicities, including serine (Ser), glycine (Gly), and leucine (Leu), into zwitterionic peptides with lysine-glutamic acid repeating units and investigated the structure and antifouling performance of the zwitterionic peptide brushes by surface plasma resonance, surface force apparatus (SFA), and all-atomistic molecular dynamics (MD) simulation techniques. Our results demonstrate that the hydrophilicity of neutral spacers alters the structure and antifouling performance of the peptide-modified surface. Hydrophilic Ser-inserted peptides reduced the interaction between the peptide monolayer and protein foulants, while hydrophobic Leu significantly increased the protein adhesion. SFA force measurements show that the presence of more spacers would increase the adhesion between the peptide monolayer and the modeling foulant lysozyme, especially for the hydrophobic spacers. MD simulations reveal that hydrophilic Ser spacers retain the hydrophilicity of the peptide monolayer and improve the antifouling performance, and Gly spacers give rise to more interchain cross-links. Leu spacers result in a more hydrophobic peptide monolayer, which leads to dehydration of the peptide monolayer and reduces the antifouling performances.

Prevalence of mental health problems in frontline healthcare workers after the first outbreak of COVID-19 in China: a cross-sectional study.

BACKGROUND: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown. METHODS: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). RESULTS: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees. CONCLUSIONS: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers.

PSMA-positive nodal recurrence in prostate cancer : Salvage radiotherapy is superior to salvage lymph node dissection in retrospective analysis.

PURPOSE: This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of 68Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE). METHODS: A total of 67 SLNRT and 33 SLND consecutive patients with pelvic and/or para-aortic nodal recurrences after RPE were retrospectively analyzed. Biochemical recurrence-free survival rates (bRFS; PSA <0.2 ng/mL) were calculated according to Kaplan-Meier and survival curves were compared using the log rank test. For multivariable analysis, binary logistic regression analysis was performed (p < 0.05). RESULTS: Median follow-up was 17 months (range, 6-53 months) in SLND patients and 31 months (range, 3-56 months) in SLNRT patients (p = 0.027). SLNRT patients had significantly more tumours of pT3 and pT4 category (82% vs. 67%; p = 0.006), pathologically involved lymph nodes (45% vs. 27%; p = 0.001) and positive surgical margins (54% vs. 12%; p = 0.001) at time of RPE than SLND patients. PSA persistence after RPE was significantly more frequently observed in the SLNRT cohort (73% vs. 27%; p = 0.001). There was no significant difference in the distribution of PET-positive lymph nodes. Median PSA before SLND was higher than before SLNRT (3.07 ng/ml vs. 1.3 ng/ml; p = 0.393). The 2­year bRFS was significantly higher in the SLNRT vs. the SLND cohort (92% vs. 30%; p = 0.001) with lower rates of distant metastases (21% vs. 52%; p = 0.002) and secondary treatments (5% vs. 39%; p = 0.011) irrespective of ongoing androgen deprivation therapy at last contact. In multivariable analysis, SLNRT was significantly associated with prolonged bRFS (regression coefficient 1.436, hazard ratio 4.204, 95% CI 1.789-9.878; p = 0.001). CONCLUSION: Based on this retrospective study SLNRT might be the preferred treatment option for patients with nodal recurrence after previous RPE.

Small-Diameter Synthetic Vascular Graft Immobilized with the REDV Peptide Reduces Early-Stage Fibrin Clot Deposition and Results in Graft Patency in Rats.

Early-stage hemocompatibility is indispensable for manufacturing tissue-engineered vascular grafts used in regenerative medicine. In this study, we report the in vivo blood response and patency of small-diameter synthetic vascular grafts modified with the Arg-Glu-Asp-Val (REDV) peptide. Vascular grafts were prepared by casting REDV-conjugated poly(depsipeptide-co-caprolactone) on a stainless-steel mandril (diameter: 1.8 mm). After implanting the grafts into the abdominal aorta of rats for 24 h, all three control grafts without the peptide and three out of the four REDV (control sequence) peptide-modified grafts showed occlusion. The luminal surfaces of these grafts were covered with thick thrombi. In contrast, all the grafts containing the REDV peptide were patent, and their luminal surfaces were covered with a thin layer of fibrin. These results indicated that the REDV peptide on the luminal surface effectively reduced early-stage fibrin clot deposition and formed the pseudo-endothelium layer in a peptide sequence-specific manner, resulting in graft patency.

Structures and Antifouling Properties of Self-Assembled Zwitterionic Peptide Monolayers: Effects of Peptide Charge Distributions and Divalent Cations.

Zwitterionic peptides are great candidates as antifouling coating materials in many biomedical applications. We investigated the structure and antifouling properties of surface-tethered zwitterionic peptide monolayers with different peptide chain lengths and charge distributions using a combination of surface plasma resonance, atomic force microscopy, and all atomistic molecular dynamics (MD) simulation techniques. Our results demonstrate that zwitterionic peptides with more zwitterionic lysine (K) and glutamic acid (E) repeating units exhibit better antifouling performance. The block charge distributions of the positive and negative charges in the peptides (having multiple positive charges next to the same amount of negative charges), although affecting the structure of the peptide molecules, do not significantly change the antifouling properties of the peptide monolayers in the solutions containing monovalent ions. However, divalent cations, Ca2+ and Mg2+, in solution can significantly alter the structure and lower the antifouling performance of the zwitterionic peptide monolayers, especially with the sequences of block charges. All atomistic MD simulations quantitatively reveal that the divalent cations in solution lead to more interchain electrostatic cross-links between peptide chains, especially for peptides with block charges, which causes dehydration of the zwitterionic peptides and diminishes their antifouling performances.