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Analyzing the influence of manufactured sand and fly ash on concrete strength through experimental and machine learning methods

Abstract River sand supplies are decreasing due to overexploitation and illicit sand mining. One ton of Portland cement production (the main binder in concrete) emits about one ton of carbon dioxide into the atmosphere. Thus, this study replaced conventional cement and river sand (R sand) with recycled waste materials (fly ash and manufactured sand (M sand)). The concrete mix proportions were designed using M40 grade, and the Ordinary Portland cement (OPC) and R sand were replaced with 0–85 wt% of fly ash and 0-100 wt% of M sand. The concrete samples were tested for compressive strength after 3–90 days of curing. Furthermore, machine learning (ML) techniques were engaged to predict the compressive strength of the concrete samples using Extreme Gradient Boosting (XGBoost), Long Short-Term Memory (LSTM), Support Vector Machine (SVM), and Gaussian Process Regression (GPR). Besides, the concrete samples containing fly ash, M sand, and R sand were characterized for microstructures and elemental compositions using SEM-EDS. The results revealed improved concrete compressive strength by incorporating fly ash and M sand. After 28 days of curing, OPC and R sand were partially replaced with 25 and 50 wt% of fly ash and M sand attained the designed strength of M 40 grade concrete. XGBoost model yielded the most accurate performance metrics for forecasting the compressive strength in training and testing phases with R2 values equal to 0.9999 and 0.9964, respectively, compared to LSTM, SVM, and GPR. Thus, the XGBoost approach can be a viable technique for forecasting the strength of concrete incorporating fly ash and M sand. SEM-EDS analyses revealed compact formations with high calcium and silicon counts. Thus, the XGBoost approach can be a viable technique for forecasting the strength of concrete incorporating fly ash and M sand.

Avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): Long-term outcomes from JAVELIN Bladder 100.

869 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1LM + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (PBC). In some cancers, the presence of DM has been associated with reduced efficacy of immunotherapy; however, data in UC are limited. We report post hoc exploratory analyses from JAVELIN Bladder 100 in pts with or without DM at randomization. Methods: Eligible pts with unresectable locally advanced or metastatic UC without progression after 1L PBC were randomized 1:1 to receive avelumab + BSC or BSC alone. The primary endpoint was OS measured from randomization; secondary endpoints included PFS measured from randomization and safety. Results: At randomization in the avelumab + BSC (n=350) and BSC alone (n=350) arms, 55 (15.7%) and 59 (16.9%) pts had documented controlled DM, and 295 and 291 pts did not have documented DM, respectively. Median follow-up in both arms was ≥38.0 months (data cutoff, June 4, 2021). In pts with or without DM, OS and PFS (investigator assessed) were prolonged with avelumab + BSC vs BSC alone (Table). In the safety analysis set of avelumab-treated pts with (n=54) or without (n=290) DM, respectively, treatment-related adverse events (AEs) of any grade occurred in 75.9% and 78.6% (grade ≥3 in 24.1% and 18.6%) and led to avelumab discontinuation in 9.3% and 12.1%; immune-related AEs of any grade occurred in 31.5% and 32.4%. Limitations include the exploratory nature of the analysis and the potential for missing DM diagnosis. Conclusions: In exploratory analyses, avelumab 1LM was associated with long-term efficacy and consistent safety in pts with aUC with or without DM. Clinical trial information: NCT02603432 . Pts with DM Pts without DM Avelumab + BSC (n=55) BSC alone (n=59) Avelumab + BSC (n=295) BSC alone (n=291) Median OS (95% CI), months 20.8 (18.0-32.4) 14.5 (11.7-21.3) 24.7 (19.9-30.0) 15.8 (13.3-18.7) 2-year OS (95% CI), % 44.5 (30.7-57.3) 34.1 (22.2-46.3) 50.7 (44.8-56.4) 39.4 (33.6-45.2) 3-year OS (95% CI), % 33.1 (20.4-46.4) 20.3 (10.8-31.9) 36.6 (30.6-42.6) 31.9 (26.3-37.7) Hazard ratio (95% CI) 0.60 (0.37-0.95) 0.78 (0.64-0.96) Median PFS (95% CI), months 5.6 (3.7-9.3) 2.0 (1.9-3.7) 5.4 (3.8-7.2) 2.1 (1.9-3.5) 2-year PFS (95% CI), % 18.5 (9.1-30.6) 9.2 (3.4-18.6) 24.3 (19.3-29.7) 6.5 (3.8-10.2) 3-year PFS (95% CI), % 13.5 (5.5-25.1) 5.5 (1.4-13.8) 16.3 (11.7-21.6) 5.3 (2.9-8.9) Hazard ratio (95% CI) 0.50 (0.33-0.77) 0.54 (0.45-0.65)

Tislelizumab in combination with abiraterone/enzalutamide for metastatic castration-resistant prostate cancer with intraductal adenocarcinoma of the prostate after progression on prior androgen receptor pathway inhibitor.

TPS299 Background: Intraductal adenocarcinoma of the prostate (IDC-P) serves as an aggressive pathological pattern of prostate cancer. Previous retrospective study suggested limited therapeutic response of chemotherapy and androgen depriving therapy for patients with IDC-P. No standard of care treatment options are established for this type of tumor. IDC-P was characterized by genomic instability, high homologous recombination repair (HRD) scores and mutational enrichment of mismatch repair (MMR) pathway, which are predictive for response to immune checkpoint inhibitor. Tislelizumab, an investigative anti-PD-1 antibody, has demonstrated disease stabilization capacity to multiple advanced tumors. Thus in this study, we aim to investigated the efficacy and safety of tislelizumab in combination with androgen receptor pathway inhibitor (ARPI) in metastatic castration-resistant prostate cancer patients (mCRPC) after failure of first-line novel hormone therapy regimens. Methods: This is a phase II, multisite, open label study with one cohort. Eligible patients must have pathologically confirmed IDC-P. Patients with any component of neuroendocrine tumor are ineligible. Patients must have received one prior type of novel hormone therapy (e.g., abiraterone, enzalutamide) in mCRPC stage . Patients receiving chemotherapy in the mCRPC stage are excluded. Participants will receive tislelizumab 200mg IV every 21 days in combination with ARPI change (abiraterone 1000 mg PO QD+ prednisone 5 mg PO BID/enzalutamide 160 mg PO QD) for four cycles. The primary endpoint is prostate specific antigen progression-free survival (PSA-PFS) and radiographic PFS (rPFS), with key secondary endpoints including PSA response and overall survival (OS). Exploratory objectives include analyzing DNA and RNA sequencing of tumors, and measurement of ctDNA and TMB. Clinical trial information: ChiCTR2400085267 .

Muscle invasive bladder cancer treatment selection in an emerging treatment era: A patient preference study.

753 Background: Patients with muscle invasive bladder cancer (MIBC) face a preference-sensitive choice among various treatment alternatives. MIBC is typically treated with radical cystectomy (RC) or bladder-sparing chemoradiation, but systemic therapy also plays a conjunctive role in reducing recurrence rates. This study elicited preferences for available and emerging systemic treatments among MIBC patients in the United States. Methods: Patients with self-reported MIBC participated in an online survey. A discrete-choice experiment elicited preferences for attributes of existing and emerging systemic treatments that could be administered with either RC or bladder-sparing approaches. Evidence-based attributes (and levels) included timing and duration of therapy (3 months before and/or 9-12 months after primary treatment); time in delaying cancer recurrence (20-64 months); overall survival (OS) rate at 5 years (40%-85%); chance of treatment-related adverse events (AEs), including fatigue (from none to moderate-severe), neuropathy (from none to moderate-severe), and risk of immune-related AEs that require oral steroid treatment (0%-25%). Conditional relative importance of attributes and risk tolerance were calculated from random-parameters logit models. In addition, direct-elicitation questions offered choices between fixed profiles of bladder-sparing treatment and RC with adjuvant and neoadjuvant systemic treatments. The Shared Decision Making (SDM) Questionnaire (SDM-Q-9) was also included, revealing patients’ levels of satisfaction with previous real-world choices. Responses to the fixed-profile questions and SDM-Q-9 were analyzed descriptively. Results: 202 participants completed the survey. Of the treatment attributes and levels evaluated, improvements in efficacy were most important (OS at 5 years, followed by delaying cancer recurrence). The average patient was tolerant of AEs and willing to accept high levels of risks (greater than those presented in the survey) and severity for any of the OS improvements offered. Two-thirds of respondents (66.8%) preferred RC plus neo- and adjuvant intravenous treatment in a profile with a 25-percentage-point increase in OS at 5 years, a 40-month delay in recurrence, and a 15% risk of immune-related AEs, mild fatigue, and nerve damage over a bladder-preserving treatment with chemoradiation and no AEs. Almost 20% of respondents disagreed with the statement “My doctor asked me which treatment option I prefer” when reflecting on their SDM experiences. Conclusions: Improving OS and delaying recurrence were the most important attributes to patients in this sample, and patients were willing to accept clinically relevant treatment-related AEs for the improvements in efficacy. Patients demonstrated heterogeneous preferences; efforts to promote shared decision-making are therefore warranted.

Comprehensive proteomic profiling of plasma samples associated with response or resistance to immune checkpoint inhibitors (ICI) in patients with renal cell carcinoma (RCC).

562 Background: ICI-based therapies are the cornerstone of treatment for advanced RCC. While many studies have focused on tumor-based biomarkers, circulating factors play an important role in therapeutic response. This study utilized a high dimensional proteomic platform to investigate plasma proteins from RCC patients undergoing ICI-based therapies to identify potential biomarkers associated with treatment outcomes. Methods: A total of 43 plasma samples (n = 40 clear cell; n = 3 non-clear cell) were collected from 33 advanced RCC patients, with 16 paired samples (pre- and post-treatment) from 6 patients and 27 unpaired samples. The cohort included patients treated with ICI monotherapy (n = 22), ICI + ICI (n = 13), ICI + VEGF inhibitors (n = 7), and ICI + CCR2/CCR5 antagonist (n = 1). For this study, we analyzed pre-treatment samples from responders (R) (n = 8; complete or partial responses), and non-responders (NR) (n = 4; progressive disease). We performed plasma proteomic analysis using the SomaScan 11k proteomic platform, and Mann-Whitney U-test comparisons between ICI-naïve samples of R and NR groups. We also performed a paired test between ICI-naïve and ICI-exposed samples in R (n = 3 patients with paired samples). Nominal p-values are reported. Results: All 43 samples passed quality control. In ICI-naïve samples, we observed that ICAM1 and ITIH3 levels were significantly higher in R compared to NR (p = 0.016 for both). Conversely, CILP2 and leptin were significantly elevated in NR (p = 0.016, p = 0.004, respectively). Further analysis for treatment evolution through paired samples showed that PD-1, CXCL9, and HLA-B were significantly elevated in ICI-exposed samples compared to ICI-naïve samples in R (p = 0.021, p = 0.022, p = 0.041, respectively). Conclusions: Our exploratory proteomic analysis identified higher ICAM1 and ITIH3 levels in ICI responders, which may reflect anti-tumor inflammation and the recruitment of immune cells to tumors. Elevated CILP2 and leptin levels were observed in ICI non-responders, highlighting their potential contributions to an immunosuppressive environment through Tregs and the TGF-β pathway. Beyond the potential biomarkers, the post-ICI elevation of CXCL9 and HLA-B in responders suggests that these may be linked to sustained immune activation during treatment, offering a foundation to understand treatment evolution in RCC.

Enhanced near-infrared photoresponse of SnS2 nanosheets by Er–Yb co-doping

Rare earth (RE) ions are important dopants to modulate semiconductor properties because of their abundant energy levels. Herein, a simple Er–Yb co-doping strategy was developed to enhance the near-infrared optoelectronic properties of SnS2 nanosheets. The constructed device based on Er–Yb co-doping SnS2 has a detectivity of ∼4.97 × 108 Jones at 980 nm. The enhanced photoresponse of the doped system at 980 nm could be attributed to the upconversion behavior of the Er–Yb ion pairs. The Yb3+ ions as sensitizers significantly enhance the upconversion emission and near-infrared photoresponse properties of the material. The energy transfer from Yb3+ to Er3+ ions can occur between different layers of co-doping nanosheets by investigating the properties of the constructed SnS2:Er/SnS2:Yb homojunction nanosheets. Density functional theory calculations reveal that Er or Yb doping introduces slight structural and charge distribution changes owing to the similarity in the metal–atom coordination structure between SnS2 and RE sulfide. Our study demonstrates that RE doping is an effective way to improve the near-infrared photoresponse of 2D materials and clarifies the relationship between luminescence and photoelectric properties.

Flowing between gongs: Mixed-methods insights into shared flow and temporal distortion in music performance

Ideas of temporal distortion prevail in the discourse of flow research, where references are often made to “time flying”. Nonetheless, little research has investigated how flow affects time perception in terms of both directionality and surrounding context, particularly within shared flow. Simultaneously, temporal distortion during music listening has been explored, but little is known about how time is experienced by performers. With this in mind, we aimed to investigate whether time distortion is associated with the experience of shared flow state, and the awareness participants have towards influencing factors on such experiences, in the context of music performance. Four groups of Javanese gamelan ensembles (total N = 36, age in years M = 44.83, SD = 14.993, 47.2% female), played in three conditions. We collected qualitative and quantitative data; focus groups and follow-up surveys explored understandings of shared flow and time, while questionnaires included pre-validated scales and an item requiring participants to estimate how much time they thought had passed. Qualitative and mixed methods findings suggest an optimal middle ground of conditions for “time flying” to occur, akin to flow state. Meanwhile, quantitative results indicate a complex relationship between temporal distortion and shared flow, whereby the relationships are opposed under two shared flow factors.

Molecular characterization of some multidrug resistant Candida Auris in egypt

Abstract Candida auris is an emerging multidrug-resistant yeast that causes healthcare-associated and deep-seated infections. Notably, the emergence of this yeast is alarming as it exhibits resistance to azoles, echinocandins, and amphotericin B, which may lead to clinical treatment failure in patients. This study aims to identify and characterize the genetic determinants of antifungal resistance in C. auris among some local clinical isolates to contribute for understanding the molecular epidemiology of C. auris in Egypt. Four test strains were identified based on the ribosomal internal transcribed spacer (ITS) region sequence and phylogenetic analysis. Antifungal susceptibility was determined using the VITEK 2 system. Molecular analysis of ERG11, ERG3, FKS1, and FKS2 was used to identify mutations associated with antifungal resistance. The four test strains were identified as C. auris. Evolutionary analysis was conducted, and sequences of ITS regions were submitted to GenBank. The mutations Y132F in ERG11 and F635Y in FKS2 were identified, which are known to confer resistance to azoles and echinocandins, respectively. The emergence of C. auris in Egypt represents a public health concern. Hospitals should implement strict infection control measures to prevent its spread. Effective treatment guidelines and ongoing monitoring of antifungal resistance are essential to combat this emerging pathogen.

The influence of body composition on the survival of patients with metastatic clear cell renal carcinoma (mccRCC) treated with nivolumab (nivo) + ipilimumab (ipi).

545 Background: Over the last decade, immune checkpoint therapy (ICT) has become the cornerstone of first-line treatment for mccRCC. Despite the widespread use, there is heterogeneity in tumor response to ICT, and there is growing interest in how host factors modulate the tumor microenvironment. Recent studies in patients with mccRCC and other malignancies suggest that ICT may be more effective in patients with higher body mass index (BMI). Since BMI is an imperfect surrogate for distinct compartments of adipose tissue and muscle, we investigated the influence of body composition on outcomes with first-line (1L) nivo + ipi in patients with mccRCC. Methods: A retrospective analysis was conducted on patients with mccRCC at MD Anderson Cancer Center from June 2015 to Dec 2021 who received nivo + ipi as 1L treatment for advanced or mccRCC. Clinical data including demographics, BMI, and IMDC risk score were collected. Body composition was measured using an AI segmentation tool at the L3 vertebra from a pre-treatment CT scan obtained within 45 days of starting nivo + ipi. Efficacy endpoints of interest were time to treatment discontinuation (TTD), progression-free survival (PFS) and overall survival (OS). We constructed flexible multivariable Cox regression models guided by directed acyclic graphs to flexibly model the association of treatment outcomes with body composition measures as continuous variable, including nonlinear terms as cubic splines, and adjusting for IMDC risk and sarcomatoid dedifferentation as confounders. Results: 209 patients received 1L nivo + ipi (78.5% male, median age of 61 years, 59.3% and 32.5% IMDC intermediate- and poor-risk). Increasing skeletal muscle mass (SMMi) was associated with inferior PFS (HR 1.52, 95% CI 1.01 - 2.31 for 1-unit increase), whereas BMI and adiposity measures were not associated with PFS. Body composition measures were not significantly associated with OS, yet noteworthy trends were observed for visceral adiposity (VATi, HR 0.69, 95% CI 0.42 - 1.15 for 1-unit increase) and SMMi (HR 1.22, 95% CI 0.72 - 2.07). Conclusions: In a large cohort of patients with mccRCC, skeletal muscle mass was surprisingly associated with inferior PFS on 1L nivo + ipi. These results build upon conflicting body composition studies in mccRCC and suggest that future studies should investigate how skeletal muscle influences the tumor microenvironment.

Real-world persistence and adherence to relugolix (REL) in US patients with nonmetastatic (nm) vs metastatic (m) prostate cancer (PC).

88 Background: REL is the only oral androgen deprivation therapy (ADT) for patients (pts) with PC, offering an alternative to long-acting injectable/implantable formulations. Intermittent ADT is often used in pts with biochemically recurrent nmPC, whereas continuous ADT is the backbone of treatment (Tx) for pts with mPC. Given potential differences associated with adherence to an oral ADT, we assessed Tx adherence and persistence stratified by presence of metastases in pts with PC treated with REL. We hypothesized REL adherence would be high in both cohorts while persistence would be shorter in pts with nmPC vs mPC. Methods: A retrospective cohort study was conducted using the Medicare fee-for-service claims database (Dec 2019–Dec 2023). Adult males with >1 claim for PC who filled ≥2 REL prescriptions and had continuous Medicare coverage ≥1 year before and ≥3 months (mo) following REL initiation (index), when claims for metastatic diagnosis could be identified, were included. Pts were categorized into nmPC vs mPC cohorts. Persistence on REL was measured from time of Tx initiation (first pharmacy claim) to discontinuation (earliest of: switch to a different ADT, Tx gap ≥60 days between REL claims, death, or end of follow-up). REL adherence was measured using proportion of days covered (PDC) for pts persistent through fixed time periods (6- and 12-mo). PDC was defined as the percentage of individual days that pts had access to REL (based on prescriptions filled and days supplied). “Adherent” was defined as PDC of ≥80%. Results: The study included 5274 pts initiating REL; mean (SD) age was 75 (±7) years; 32% had mPC. Follow-up was similar in pts with nmPC and mPC (Table). Persistence on REL was shorter for nmPC vs mPC (median, 7 vs 9 mo; log-rank P <0.001). Across both cohorts, the vast majority of pts had PDC ≥80% (nmPC, 95%; mPC, 94%). Of those persistent at 6 mo, 95% across both cohorts had PDC ≥80%. Of those persistent at 12 mo, 97% had PDC ≥80% (nmPC, 98%; mPC, 96%). Conclusions: In this real-world study, among pts with PC who persisted on REL,high treatment adherence was observed, regardless of disease state (nmPC and mPC). Pts with mPC persisted on REL therapy longer compared to those with nmPC (median 9 vs 7 mos). Further research is needed to understand what other characteristics are associated with persistence on REL. Total(N=5274) nmPC with REL(n=3603) mPC with REL(n=1671) Follow-up (mo), mean ± SD [median] 16 ± 9 [15] 16 ± 9 [14] 16 ± 9 [15] Persistence on therapy (mo), mean ± SD [median] 10 ± 7 [7] 9 ± 7 [7] 11 ± 8 [9] Overall PDC, mean ± SD [median] 96 ± 10 [99] 97 ± 10 [99] 96 ± 11 [98] Overall PDC ≥80%, n (%) 4990 (95) 3424 (95) 1566 (94) Pts with ≥6 mo of persistence, n 3870 2617 1253 PDC ≥80% at 6 mo, n (%) 3676 (95) 2486 (95) 1190 (95) Pts with ≥12 mo of persistence, n 1830 1131 699 PDC ≥80% at 12 mo, n (%) 1775 (97) 1104 (98) 671 (96)

Erratum: Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors

Efficacy of neoadjuvant/induction (NAC) chemotherapy in nonmetastatic muscle-invasive bladder cancer treated with chemoradiotherapy (CRT): A systematic review and meta-analysis.

814 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the established standard for nonmetastatic muscle-invasive bladder cancer (MIBC). However, bladder-sparing approaches using chemoradiotherapy (CRT) offer comparable outcomes. While NAC has proven beneficial before RC, its value prior to CRT remains uncertain. This systematic review and meta-analysis aimed to evaluate the impact of NAC on outcomes in patients undergoing CRT for bladder preservation. Methods: A comprehensive search of PubMed, Embase, and Cochrane databases was conducted to identify studies comparing NAC plus CRT versus CRT alone in MIBC. Both randomized controlled trials (RCTs) and observational studies were eligible. Studies with overlapping populations or non-English publications were excluded. Heterogeneity was assessed with I² statistics, and all analyses were performed using random-effects models in Review Manager 5.4.1. The study was registered in PROSPERO (CRD42024590258). Results: Four observational studies, encompassing 3,354 patients, were included as no RCTs met the inclusion criteria. NAC was administered to 656 patients (19.5%). Median follow-up ranged from 15.9 to 74.4 months. All patients in the NAC group received platinum-based chemotherapy (MVAC, ddMVAC, GC, or CMV). Concurrent CRT regimens included cisplatin, gemcitabine, or mitomycin with radiotherapy. No significant difference in overall survival was observed between NAC + CRT and CRT alone (HR = 0.99, 95% CI 0.87–1.13, p = 0.89, I² = 0%). Disease-free survival data were available from two studies, showing no significant difference (HR = 1.07, 95% CI 0.57–2.01, p = 0.82, I² = 39%). All included studies had a serious risk of bias, mainly due to confounding and selection bias, as assessed by the ROBINS-I tool. The overall certainty of the evidence was rated as very low using the GRADE framework. Conclusions: Our analysis found no survival benefit from adding NAC to CRT in patients with MIBC. However, the quality of the evidence is very low, largely due to the retrospective nature of the data. Further randomized clinical trials are needed to clarify the role of NAC in bladder preservation strategies.

All-implanted lateral β-Ga2O3 MOSFET devices realized on semi-insulating (-201) β-Ga2O3 substrates

In this work, we report on the fabrication of all-implanted β-Ga2O3 metal-oxide-semiconductor field-effect transistor (MOSFET) devices on semi-insulating (-201) β-Ga2O3 substrates. Through the use of multiple energy Si+ implantation and subsequent annealing, we were able to achieve high activation efficiencies up to 87% allowing to realize the active transistor channel and Ohmic contact regions with electrical properties comparable to homoepitaxial layers grown by metal-organic chemical vapor deposition. The fabricated β-Ga2O3 MOSFET devices featured excellent current modulation with on/off current ratios up to 109, maximum drain current densities of 180 mA/mm, and specific on-resistances of 1.5 mΩcm2. Furthermore, breakdown measurements in air of the non-field-plated MOSFET devices with a gate-to-drain distance of 2 μm showed a catastrophic breakdown at 332 V, which equals an average breakdown strength of 1.7 MV/cm. The outcome of this work emphasizes the high potential of this all-implantation approach for fabricating high-performing Ga2O3-based electronic devices for next-generation power electronics applications without the need of sophisticated high-quality epitaxial growth.

HybridBranchNetV2: Towards reliable artificial intelligence in image classification using reinforcement learning

Many artificial intelligence (AI) algorithms struggle to adapt effectively in dynamic real-world scenarios, such as complex classification tasks and object relationship extraction, due to their predictable but non-adaptive behavior. This paper introduces HybridBranchNetV2, an optimized hybrid architecture designed to address these challenges. The key novelty of our approach lies in the integration of reinforcement learning for adaptive feature extraction and the use of graph-based techniques to analyze object relationships in complex environments. By dynamically adjusting feature extraction based on feedback from the environment, the model improves adaptability, while graph-based methods allow for a more comprehensive analysis of object relationships. Our extensive evaluations demonstrate that HybridBranchNetV2 achieves average 91.75% accuracy over four different challenging datasets. In particular, a 14% improvement obtained on the Visual Genome dataset and ImageNet 1K compared to the original HybridBranchNet model. Additional testing on CIFAR, Flowers, and ImageNet datasets revealed improvements of 6%, 1%, and 6%, respectively. These advancements not only enhance classification accuracy but also ensure efficient computation, making HybridBranchNetV2 suitable for real-time applications with minimal risk of overfitting. The proposed framework demonstrates significant improvements in adaptability, performance, and computational efficiency, addressing critical limitations in current AI models.

Optimal scheduling of solar powered EV charging stations in a radial distribution system using opposition-based competitive swarm optimization

Real-world analysis of pembrolizumab utilization and characteristics of patients being prescribed treatment in early stage RCC.

480 Background: In the United States, adjuvant pembrolizumab was approved on November 17, 2021, for patients with RCC with intermediate-high (T2N0M0-G4, T3N0M0, any grade) or high risk (T4, any grade; N+, any T, any grade; and M1NED patients) of recurrence following nephrectomy. This study aims to assess adoption of adjuvant pembrolizumab in routine practice and demographic and clinical characteristics of post nephrectomy RCC patients who received this therapy. Methods: This retrospective study included adult patients with non-metastatic localized RCC who underwent nephrectomy between November 17, 2021, and December 31, 2022, and were seen in the U.S. Oncology Network. Patients were excluded if they were treated for other documented primary cancer diagnoses or enrolled in clinical trials. Descriptive analyses were conducted to evaluate demographic, clinical, and treatment characteristics overall, and for patients who received adjuvant pembrolizumab monotherapy and those who did not. Multivariate logistic regression was used to identify factors associated with adjuvant pembrolizumab use. Results: In total, 178 patients were included. The mean age was 62 years (SD 11.8), with a majority being male (66.3%, n=118), and a median follow-up of 7.9 months (Q1,Q3: 4.1,9.8). The majority had intermediate-high risk (n=86, 57.5%), clear cell (cc) RCC (n=147, 82.6%) and received adjuvant pembrolizumab monotherapy (n=118, 66.3%). Among those who received adjuvant pembrolizumab, 90.7% had ccRCC, 62.5% were intermediate-high risk (T2N0G4: 8 (55.1%), T3N0 All Grades: 53 (44.9%)), 27.5% were N+ with a median follow-up of 8.3 (Q1, Q3: 6.0, 10.1) months. Median time to the start of adjuvant pembrolizumab post nephrectomy was 1.6 months (Q1, Q3: 1.3,2.1). The median time to treatment discontinuation was 11.5 months (Q1, Q3: 9.0, 11.5) (the recommended duration of treatment for adjuvant pembrolizumab is: 12 months at 17 cycles at 200mg/ Q3W or 9 cycles at 400mg/Q6W). Multivariate analysis showed that patients with non ccRCC histology were 93% less likely (p-value: <0.0001) and those whose with first oncologist visit >=2 months post nephrectomy were 60% less likely (p-value:0.035) to receive adjuvant pembrolizumab treatment. Conclusions: This study demonstrated notable uptake of adjuvant pembrolizumab among post-nephrectomy RCC patients in this community setting following FDA approval. RCC histology and the timing of oncologist visits post nephrectomy were significant factors influencing the receipt of adjuvant pembrolizumab. Future research should focus on examining referral patterns, and identifying the drivers and barriers to treatment adoption, with the goal of developing strategies to enhance its integration. Additionally, future research may explore long-term outcomes and real-world effectiveness of adjuvant pembrolizumab.

Application of radiomics as a risk stratification tool in node positive penile cancer.

3 Background: The risk level of lymph node metastasis in penile cancer is determined using the Graafland criteria which determines how patients are treated. These imaging-based criteria have critical implications on patient care yet have not been extensively validated. The purpose of this study was to validate the Graafland criteria and to assess the use of radiomics analysis of CT scans to standardize risk stratification. Methods: Thirty-eight patients with squamous cell penile cancer with CT scans prior to regional lymphadenectomy were included in this retrospective cohort. Patients with prior chemotherapy for PSCC or any inguinal and pelvic radiotherapy were excluded. All CT scans were performed using IV contrast with axial slice thickness of 3mm. CT scans were analyzed by two experienced oncologic radiologists using Graafland criteria. The largest inguinal lymph node in each patient was segmented and radiomics features were extracted and compared to pathologic evidence of high-risk disease. 308 radiomic features were identified. Features with poor predictive value (i.e. AUC <0.5) were excluded. Pearson’s correlation coefficient was used to find the clusters of features (absolute value of correlation of ≥0.95), and the most predictive feature of each cluster was selected.199 features with best predictive value were selected for analysis. Two logistic regressions were performed using stepwise selection and LASSO approach. Results: In 38 subjects, 16 of 38 patients were identified as harboring lymph node metastasis on surgical pathology. Applying Graafland criteria had an inter-reader concordance of 89.5% (34/38), an accuracy of 86.8% (95%CI: 71.9% - 95.6%); AUC: 0.869 (95% CI: 0.758– 0.981); Sensitivity 87.5%; and Specificity 86.4% in predicting high-risk disease. CT radiomics analysis yielded a model including two features F54 (compactness) and F279 (3D wavelet_P1_L2_C1) which is a multi-order texture-based feature. The logistic regression with stepwise selection included two features (F54 and F279) and had an (AUC = 0.921 ± 0.096) after five-fold cross validation. Conclusions: Graafland criteria accurately predicted the presence of high-risk nodal disease on pre-operative CT scans when assessed by expert radiologists. Radiomic analysis shows promise in further refining and standardizing the detection of high-risk nodal disease with the advantage in ease of training and/or clinical application.

Genomic alterations and their pathologic responses in high-risk localized prostate cancer (HRLPC) in subprotocol 1 of the Genomic Umbrella Neoadjuvant study (GUNS).

403 Background: GUNS (NCT04812366) is a multicenter adaptive phase II trial evaluating 24 weeks of biomarker-selected, neoadjuvant androgen receptor pathway inhibitor (ARPI) combination therapies on depth of pathologic response (complete response [pCR] or <5 mm minimal residual disease [MRD]) in HRLPC. After 8 weeks of LHRHa + apalutamide (APA), participants are assigned to 1 of 4 sub-protocols (SP) combining 16 weeks of an ARPI doublet with drugs defined by specific genomic alterations (e.g. SP-2, docetaxel for RB1 , PTEN , TP53 loss; SP-3, niraparib for DNA-repair def ; SP-4, atezolizumab for mismatch-repair def ). SP-1 randomises men without these aggressive genomic alt and includes those that enhance AR activity (ETS fusions, FOXA1 , SPOP ) to either SP-1a (LHRHa + APA) or SP-1b (LHRHa + APA + abiraterone acetate/prednisone). SP-1 tests the hypothesis that ARPI triplet intensification, in cancers with AR-associated genomic alt , will increase depth of pathologic response. Methods: From 9/2021 to 8/2024, GUNS enrolled 95 and 30 men at University of BC and Toronto, respectively. Diagnostic biopsies underwent Tempus’ CLIA-certified 648-gene panel DNA sequencing (seq) and whole-transcriptome RNA-seq. This analysis focuses on 46 men enrolled to the 1 st stage of SP-1 who completed neoadjuvant therapy and surgery. Results: DNA-seq from 105/125 patients reveals a genomic landscape dominated by AR-associated alterations ( 36% ETS fusion, 23% FOXA1, 13% SPOP ). Other frequently altered genes were TP53 (14%), PTEN (12%), and BRCA2 (9%). Transcriptomes largely cluster in alignment with ETS fusions and SPOP status. ETS fusions were associated with PCS2-luminal-subtype and decreased proliferative signatures, whereas most other genomic alt were associated with PCS1-luminal-subtype. AR signatures associated with SPOP and FOXA1 mutations but not ETS fusions. 46 men, equally balanced for high-risk features and genomic alt , were randomized to SP-1a or SP-1b. Undetectable pre-surgery PSA levels trended higher in SP-1b (16/23) vs. SP-1a (11/23), but was not statistically significant (p = 0.12). While there were no pCR, MRD rates were significantly higher in SP-1b compared to SP-1a (43% vs 13%, p=0.012, odds ratio = 5.9). Degenerative scores (morphologic indicators of treatment stress) also averaged higher in SP-1b vs. SP-1a. Positive margin (17%) and lymph node (35% vs 26%) status were similar in both arms. Although genomic PTEN alt were assigned to SP-2, 7 patients in SP-1 were found to be PTEN neg by IHC and 6 were non-MRD; PTEN-IHC neg trended more common in non-MRD (21%) than MRD (8%) cases. Conclusions: SP-1 associated genomic alt (ETS fusion, FOXA1, SPOP) are the most frequent alterations in GUNS. Significantly higher rates of MRD in SP-1 patients treated with an ARPI triplet vs. doublet are of interest and support further evaluation with 2 nd stage expansion. Clinical trial information: NCT04812366 .

Assessing practice gaps and challenges for immunotherapy integration in treatment of metastatic urothelial carcinoma.

694 Background: The approval of pembrolizumab with enfortumab vedotin in the first-line setting has shifted the treatment paradigm for patients with metastatic urothelial carcinoma (mUC). However, integrating these novel therapies into clinical practice can be challenging for health care providers (HCPs). To better understand real-world challenges and barriers for integrating immunotherapy in routine practice, we surveyed providers across community-based oncology settings. Methods: Between 02/2024 and 04/2024, multidisciplinary (MDT) oncology team members (N = 60) across the US were surveyed to assess providers' current practices and challenges regarding biomarker testing, immunotherapy use, and multidisciplinary coordination in mUC care. Teams then participated in a network-wide workshop to develop action plans for improving mUC care. Results: HCPs reported ongoing challenges in integrating novel therapies in clinical practice, including individualizing treatment plans and sequencing (28%), keeping up with clinical evidence (24%), and differentiating available immunotherapy and combination regimens (14%). Additionally, HCPs reported challenges in providing patient-centered supportive care (12%) and engaging patients in shared decision-making (10%). Most HCPs routinely tested for PD-L1 (82%), HER2 expression (63%) and alteration (55%), and FGFR (62%) , and <50% tested PIK3CA and CDKN2A alterations. While HCPs felt confident in applying the latest guidelines to treatment selection (62%), only 45% of cisplatin-ineligible patients were reported to have received approved first-line immunotherapy combination in the metastatic setting. Most HCPs felt confident recognizing and managing immune-related adverse events (64%) and reported that only 15% of patients required treatment discontinuation due to adverse events. Only 21% of HCPs were fully satisfied with MDT coordination/communication and believed that improving MDT collaboration (33%) and provider education on integrating immunotherapy and combination approaches (31%) would most improve mUC care. After participating in a network-wide workshop, teams developed action plans including improving MDT coordination, standardizing and streamlining biomarker testing, and increasing education on treatment sequencing guidelines. Following integration of these action plans, 100% of HCPs reported improved/increased alignment with evidence-based guidelines. Additionally, HCPs reported increasing provider education on integrating immunotherapy and combination therapies into practice (71%) and improving MDT collaboration (71%). Conclusions: These data and actionable insights can inform future targeted initiatives to improve integration of evidence-based immunotherapy and combination targeted agents into practice for patients with mUC.

Terahertz near-zero reflection modulator based on cascaded electrical length reconfiguration

Return loss is a core indicator of module connectivity performance in integrated communication systems. Reflections from the modulation device can cause power fluctuations, leading to excessive amplitude noise affecting the system's signal-to-noise ratio. To solve the problem of high return loss in existing terahertz amplitude modulation techniques, this paper proposes a near-zero reflection terahertz modulator based on an electrical length reconfiguration cascade. The ON-OFF effect of the modulator is achieved through the cascade's electrical length reconstruction, and the reflections are effectively suppressed from the ON state to the OFF state. Experimental results demonstrate that the proposed modulator achieves a broadband low-reflection effect in the 170–260 GHz band, with a Voltage Standing Wave Ratio (VSWR) of less than 1.5 over a bandwidth of 60 GHz and an optimal VSWR of 1.1. It has the potential to support high-speed response as well as the large-capacity, high-rate data transmission. Accordingly, the proposed modulator offers a promising solution for the design of high-performance terahertz modulators and multi-channel integrated terahertz communication systems.