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Abstract Background and Objective Management of von Hippel–Lindau (VHL) disease is challenging due to multisystem involvement and limited systemic treatment options. Belzutifan has shown promising efficacy in clinical trials; however, real-world data remain limited. We aimed to evaluate its effectiveness and safety in a real-world cohort. Methods We conducted a retrospective study of 59 patients with VHL disease treated with belzutifan between August 2021 and January 2026. Objective response rates (ORR) for renal cell carcinoma (RCC), central nervous system hemangioblastomas (CNS HB), and pancreatic neuroendocrine tumors (pNET) were assessed by an independent radiologist. Retinal hemangioblastoma outcomes were evaluated through ophthalmology records by chart review. Results Median follow-up was 29 months. ORR was 27.6%, 39.6%, and 85.7% for RCC, CNS HB, and pNET, respectively. Among 13 patients with retinal hemangioblastomas (20 eyes), 17 eyes (85%) showed improvement. At data cutoff, 47 patients (79.6%) remained on treatment, while 12 (20.3%) discontinued (7 due to adverse events, 3 to disease progression, and 2 to other reasons). The most common adverse event was anemia (86.4%). Grade ≥3 events occurred in 10 patients (16.9%). The procedure rate per patient-year decreased from 0.35 in the 3 years prior to treatment to 0.08 during follow-up (Incidence Rate Ratio, 0.23; 95% CI, 0.12–0.47; P < 0.001) Conclusions Belzutifan demonstrated efficacy across VHL-associated lesions, with favorable safety profile. Most adverse events were grade 1–2. A reduction in procedure rate was observed after treatment initiation.

Abstract Clinical empathy is essential for patient care, but physicians need continually balance emotional warmth with factual precision under the cognitive and emotional constraints of clinical practice. This study investigates how large language models (LLMs) can function as empathy editors, refining physicians’ written responses to enhance empathetic tone while preserving underlying medical information. More importantly, we introduce novel quantitative metrics, an Empathy Ranking Score and a MedFactChecking Score to systematically assess both emotional and factual quality of the responses. Experimental results show that LLM-edited responses significantly increase perceived empathy while preserving factual accuracy compared with fully LLM-generated outputs. These findings suggest that using LLMs as editorial assistants, rather than autonomous generators , offers a safer, more effective pathway to empathetic and trustworthy AI-assisted healthcare communication.

483 Background: Sarcomatoid dedifferentiation (sRCC) in metastatic clear-cell renal cell carcinoma (mccRCC) confers aggressive disease and poor prognosis. We maintain a living meta-analysis of first-line immune checkpoint inhibitor (ICI)–based combinations in mccRCC (Riaz et al., Eur Urol Oncol 2021), which demonstrated improved survival with ICI-based regimens over sunitinib. Here, we present an updated synthesis focused on the comparative efficacy of ICI combinations in the sarcomatoid subset. Methods: A systematic search of MEDLINE, EMBASE, and CENTRAL through October 2025 was performed as part of our living meta-analysis of first-line mccRCC therapy. Eligible phase III RCTs compared ICI combinations (IO/IO or IO/TKI) versus sunitinib, including CheckMate 214, CheckMate 9ER, KEYNOTE-426, CLEAR/KEYNOTE-581, JAVELIN Renal 101, and IMmotion151. Extracted outcomes included overall (OS) and progression-free survival (PFS), and objective (ORR), complete (CR), and partial (PR) response rates. Random-effects meta-analyses generated pooled hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) for response rates with 95% confidence intervals. Subgroup interaction analyses compared sarcomatoid versus non-sarcomatoid subgroups, with p < 0.1 considered significant. Results: Six phase III RCTs (n = 5,121; 624 sarcomatoid) were included. Across all ICI-based combinations, ICI therapy improved outcomes versus sunitinib in both sarcomatoid and non-sarcomatoid disease. In the pooled analysis, the OS interaction favored sRCC meeting the prespecified significance threshold for subgroup analyses (HR 0.53 vs 0.68; p-interaction = 0.06 < 0.10), while no significant interaction was seen for PFS. Response outcomes showed the strongest differential benefit, particularly with IO/TKI regimens. IO/IO results were directionally consistent but limited by smaller non-sarcomatoid samples. Conclusions: ICI-based combinations significantly improve survival and response outcomes versus sunitinib in mccRCC. Using a prespecified α = 0.10 for interaction testing, the pooled analysis showed a significant OS interaction and higher response rates in sRCC, indicating enhanced ICI sensitivity. These updated meta-analysis data support ICI regimens as the preferred first-line therapy for mRCC with sarcomatoid de-differentiation. Endpoint Regimen Subgroup (S = sarcomatoid; NS = non-sarcomatoid) Effect (95% CI) p-interaction PFS IO/IO S 0.51 (0.40–0.65) – IO/TKI S vs NS 0.48 (0.36–0.64) vs 0.46 (0.39–0.52) 0.81 OS IO/IO S 0.54 (0.07–4.42) – IO/TKI S vs NS 0.51 (0.17–1.48) vs 0.68 (0.30–1.58) 0.24 ORR IO/IO S 2.93 (0.49–17.37) – IO/TKI S vs NS 2.43 (1.84–3.21) vs 1.95 (1.67–2.28) 0.03 CR IO/IO S 3.81 (0.82–17.71) – IO/TKI S vs NS 5.93 (4.73–7.42) vs 2.85 (0.10–83.73) 0.007 PR IO/IO S 3.48 (1.70–7.11) – IO/TKI S vs NS 2.10 (1.78–2.47) vs 1.75 (1.18–2.61) <0.001

464 Background: Based on LITESPARK-005 trail, Belzutifan was FDA-approved to treat advanced RCC following ICI and a VEGF-TKI. We conducted a retrospective cohort study to report the real-world outcomes of Belzutifan in pre-treated RCC patients. Methods: A retrospective chart review of all patients who received Belzutifan at the Mayo Clinic Comprehensive Cancer Center between Dec 2023 and Sep 2025 was conducted. Patients treated for sporadic RCC were eligible; those with von Hippel–Lindau disease, non-RCC pathologies (e.g., Pheochromocytoma, ovarian cancer) were excluded. Radiologic response was assessed by trained curators using RECIST-defined criteria, approximated through systematic review of radiology reports with clinician adjudication when needed. Progression-free survival (PFS), defined as the time from treatment initiation to radiographic progression or death, was estimated using the Kaplan–Meier method. Non-progressors were censored at the last radiology assessment. Patients who discontinued therapy for non-progression reasons were censored at the last radiology assessment prior to discontinuation. Any-cause hypoxia and anemia were reported using CTCAEv5 definitions. Results: A total of 158 patients were identified; 83 (52.5%) who received Belzutifan for sporadic RCC were included. The remaining were excluded for VHL disease (68, 43%) or other pathologies (7, 4.4%). Median follow up was 12 months, 67% were male, median age was 70 (range 39, 94) with 57 patients (69%) were ≥ 65. 28 patients (34%) had a poor IMDC score at baseline. The cohort received a median of 3 previous lines of therapy (range 1,8). Median treatment duration was 3 months (IQR: 1-9.5). Median PFS was 5.7 months (95% CI, 3.8–8.7). At 12 and 18 months, 23.1% and 13.9% of patients, respectively, remained alive and progression-free. Corresponding OS rates at these time points were 60.2% and 51.5%. A confirmed ORR occurred in 12 patients (14.4%). Hypoxia occurred in 44 (53%) patients, median onset 31 days (range 1–270) and 29 (34.9%) required hospitalizations. Median hemoglobin (Hb) levels at baseline were 12.65 g/dl (range, 7.2-15.5), and 68 (82%) patients developed Hb decline on Belzutifan, 27 (32.5%) required transfusions. Conclusions: In an older, high-risk cohort with higher number of prior lines of therapy, Belzutifan yielded PFS/OS and ORR landmarks comparable to the trial supporting its effectiveness in the real world. Outcomes compared with LITESPARK-005 trial. Variable Real world cohort (Mayo Clinic) LITESPARK-005, Belzutifan arm Median PFS (months, 95% CI) 5.7 (3.8-8.7) 5.6 (3.9-7) 12-month PFS rate (%, 95% CI) 23.1% (14.4-33.4) 33.4% (28.4-33.5) 18-month PFS rate (%, 95% CI) 13.9% (7.7-23.9) 24% (19-29.4) 12-month OS rate (%, 95% CI) 60.2% (48.9-70.8) 67.9% (62.9-72.4) 18-month OS rate (%, 95% CI) 51.5% (40.6-62.9) 55.2% (50-60.1) ORR (%, 95% CI) 14.4% (7.7-23.9) 21.9% (17.8-26.5)

Objectives To comprehensively review the available literature on prehabilitation and rehabilitation exercise, nutrition, and psychological support interventions for patients with kidney cancer (KC), to summarise the clinically relevant efficacy and cost‐effectiveness of interventions, to expose key knowledge gaps, and to inform future investigations and initiatives. Methods This review was performed according to the per Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) Extension for Scoping Reviews Guidelines. We included randomised controlled trials (RCTs) assessing programmes of prehabilitation or rehabilitation, exercise, psychological support, or nutrition components in patients with KC or KC caregivers from January 2004 to March 2022. Statistically significant positive (SS+) and negative (SS−) results were summarised. Results The systematic search yielded 10 968 records including 18 RCTs, involving 2774 unique subjects, 706 of whom were KC patients/survivors. None included caregivers or assessed cost‐effectiveness. Two interventions were implemented before surgery, one was implemented prior to initiation of systemic therapy, eight were implemented during systemic or radiation therapy, three were implemented after treatment, while implementation time was not specified for four interventions. Conclusion Most (14/18) RCTs involving exercise, nutrition, psychological support, or prehabilitative or rehabilitative programmes for KC performed to date demonstrated SS+ results. The evidence was most robust regarding previously evaluated psychological support, especially mindfulness‐based interventions (9/10 studies demonstrating SS+ improvement in primary outcomes), followed by therapeutically valid exercise with/without psychological support (5/8 RCTs demonstrated efficacy), then nutrition or pharmacological interventions (2/5 demonstrated efficacy). Level 1 evidence supports counselling patients and referral to mindfulness‐based psychological therapy along with physical therapy or physical medicine and rehabilitation, as well as consideration of preoperative carbohydrate drinks. No studies have examined impact on caregivers, or cost‐effectiveness, which are both critical areas for future study.

5108 Background: We previously proposed a hybrid framework combining LLMs and rule based algorithm (RBA) for automating risk stratification in locPCa. Herein, we aim to validate the risk stratification agent (RSA) in a prospective cohort, develop & evaluate the treatment recommendation agent (TRA) based on NCCN guidelines, and develop an interactive interface to facilitate clinicians for accurate risk stratification and treatment recommendations at the point of care. Methods: This study included pts with locPCa (2004-2024) presenting at Mayo Clinic with at least 1 positive prostate biopsy and MRI report available. For RSA prospective validation, GPT4 extracted key phenotypic variables (PSA, T stage, prostate volume, number of cores, Gleason patterns, grade group) from unstructured MRI and biopsy reports using a zeroshot prompt. An RBA then classified pts into NCCN risk groups. The agent performance was compared with the treating clinician's documentation and evaluated against gold-standard labels manually annotated by two independent clinicians. For development of TRA, two experiments were performed using GPT4 with and without retrieval-augmented generation (RAG) to generate treatment plans. Generated treatment plans were evaluated using NCCN guideline-informed treatment decision tree based algorithm (DTA). Evaluation metrics, weighted – accuracy (acc) and F1, were computed. A clinician facing interface (lisr.org/risk) was developed to provide accurate risk stratification and treatment plans. Results: A total of 858 pts were included (500 for prospective validation, 358 for treatment recommendations). Prospective validation for RSA demonstrated a higher F1 score of 0.89 compared to the treating clinician (F1: 0.58). Treatment recommendation experiments showed that GPT4 with RAG achieved higher acc (64% full – all correct treatment options and 36% partial – at least 1 correct treatment option) compared to GPT4 alone (35% and 65%, respectively). Sensitivity analysis using DTA-informed GPT4 note generation achieved 94% full acc and 6% partial acc. GPT4 alone generated hallucinated treatment options in 71% of cases, while GPT4 with RAG reduced this to 32%. Conclusions: The multi-agent framework based on LLM and RBA achieves high accuracy in risk stratification and treatment recommendation for locPCa. A multi-agent framework with an interactive interface holds high promise to enable efficient, accurate decision-making, and improve locPCa management at the point of care Performance evaluation. RSA(acc; F1) % TRA(full acc; partial acc) % Clinician RSA* GPT4 RAG+GPT4 DTA+GPT4 Overall 60; 58 89; 89 29; 71 64; 36 94; 6 V. High 94; 33 96; 96 55; 45 69; 31 93; 7 High 46; 52 92; 89 - - - Int. Unf 80; 61 91; 90 5; 95 38; 62 93; 7 Int. Fav 57; 64 84; 87 0; 100 98; 2 100; 0 Low 57; 65 87; 80 100; 0 95; 5 90; 10 V. Low 8; 13 50; 67^ - - - *Statistical significance (p<0.01) except for ^V. Low.

454 Background: Limited data exist on outcomes in mRCC patients with major venous involvement (MVI). Assessment of impact of a given variable on prognosis in cancer patients is challenging given competing causes of death (PMID: 25417239). This analysis aims to estimate cancer prognosis in mRCC patients with MVI, considering death from competing causes. Methods: Data from the Surveillance Epidemiology and End Results (SEER) database (2010-2020) were analyzed for survival and mortality in mRCC patients with MVI. 5-year (y) overall survival (OS) and 5-y probability of cancer death were calculated using the actuarial method in SEER*Stat 8.4.4, reported as percentages with 95% confidence intervals (CI). Results were based on the site of MVI (renal vein, inferior vena cava [IVC]) and stratified by age (<65, >65 years), gender (male, female), and race/ethnicity (Non-Hispanic [NH] White, NH Black, NH Asian/Pacific Islander [API], Hispanic). Results: A total of 89047 mRCC patients were included in our analysis of whom 10785 (12%) had major venous involvement (MVI). Overall, patients who experienced MVI had worse prognosis as compared to those who did not have MVI (5-y OS: 53.2% vs 84.4% and 5-y cancer death: 38.6% vs 8.2% respectively). Among cohort with MVI, prognosis was poor with IVC involvement as compared to involvement of renal vein (5-y OS: 36% vs 57%; 5-y cancer death: 56% vs 35% respectively). Patients who had the worst prognosis with MVI included older adults (>65 y) (5-y OS: 47.8%; 5-y cancer death: 40.8%) and NH Black (5-y OS: 41.5%; 5-y cancer death: 49.8%) (Table). Conclusions: Prognosis in mRCC with MVI, especially with IVC involvement, was poor, particularly for older adults (>65 y) and NH Black patients. Further research is needed for better prognostication and risk stratification to improve outcomes for high-risk patients. Subgroup No MVI MVI N 5-year OS (%), 95% CI 5-year Cancer death (%), 95% CI N 5-year OS (%), 95% CI 5-year Cancer death (%), 95% CI Overall population 78,262 84.4 (84.1-84.7) 8.2 (8.0-8.4) 10,785 53.2 (52.0-54.3) 38.6 (37.5-39.7) Age <65 y 49,217 89.0 (88.6-89.2) 6.5 (6.3-6.8) 5,897 57.5 (56.0-59.0) 36.8 (35.4-38.3) >65 y 29,045 77.0 (76.1-77.2) 10.9 (10.5-11.4) 4,888 47.8 (46.0-49.5) 40.8 (39.2-42.4) Gender Male 49,221 83.0 (82.7-83.5) 8.9 (8.6-9.2) 7,503 53.2 (51.8-54.6) 38.3 (37.0-39.6) Female 29,041 86.5 (86.0-86.9) 7.0 (6.7-7.4) 3,282 53.0 (51.0-55.0) 39.4 (37.4-41.3) Race/ethnicity NH White 49,520 84.0 (83.7-84.4) 8.3 (8.0-8.5) 7,182 53.5 (52.1-54.8) 38.0 (36.7-39.3) NH Black 8,878 82.0 (81.0-82.9) 8.1 (7.5-8.8) 685 41.5 (37.1-45.9) 49.8 (45.4-54.1) NH API 4,747 86.0 (85.1-87.4) 8.5 (7.6-9.4) 713 52.9 (48.2-57.3) 39.9 (35.5-44.1) Hispanic (All Races) 13,826 86.5 (85.8-87.2) 7.9 (7.4-8.4) 2,014 56.2 (53.4-58.8) 36.7 (34.1-39.2) N: number of cases; OS: overall survival; CI: confidence interval; NH: Non-Hispanic; API: Asian/Pacific Islander; MVI: major venous involvement.

520 Background: The annual incidence of renal cancer is 0.02% among the general United States population. End stage renal disease (ESRD) and exposure to dialysis are thought to be the primary drivers of increased risk of renal cancer in renal transplant patients rather than immunosuppression. This has been evidenced by how the incidence of RCC in heart transplant recipients is no different than the normal population. In this study, we aim to characterize RCC incidence among kidney transplant patients (usually exposed to ESRD/dialysis) versus other solid organ transplant patients (usually unexposed to ESRD/dialysis). Methods: We used CPT codes to search for patients who had received a solid organ transplant (kidney, liver, heart, lung, pancreas) at all Mayo Clinic sites from 1/1/2018 to 1/1/2024. Within this cohort, we identified those who had been diagnosed with kidney cancer after initiating dialysis or receiving a transplant, and retrospectively extracted data related to demographics, cancer diagnosis, and transplant details. Results: We identified 10873 patients who had received a solid organ transplant (Table 1). Of these, 178 (1.76%) were diagnosed with kidney cancer after either starting dialysis or receiving a transplant. These 178 patients were of median age 56 years at time of cancer diagnosis (STD 12), 71% male, 70% white, 20% black, 4.5% Asian, 2.8% American Native. Of 5792 patients who had received a kidney transplant (with or without another solid organ transplant), 172 (2.97%) were diagnosed with kidney cancer after having started dialysis or receiving a kidney transplant. Of these 172, 156 (91%) were exposed to dialysis (107 primarily hemodialysis and 48 peritoneal). Of 4392 patients who had received a solid organ transplant other than kidney (liver, heart, lung, and/or pancreas), 6 (0.14%) were diagnosed with kidney cancer after having received a kidney transplant. Of these 6, none underwent dialysis. Conclusions: Patients with kidney transplants are at increased risk of kidney cancer compared to patients with non-kidney solid organ transplants (2.97% vs 0.14%). This supports prior evidence showing ESRD plays a significant role in the pathogenesis of kidney cancer. Patients who received solid organ transplants at Mayo Clinic from 2018-2024 and were subsequently diagnosed with kidney cancer. n % With RCC after TXP 178 1.7587% Cancer Diagnosis after Kidney HD/TXP 172 2.9696% Cancer Diagnosis after Other TXP 6 0.1386% Patients who received solid organ transplants at Mayo Clinic from 2018-2024 n % Unique Patients 10121 100% Kidney Transplant 5792 57.23% Alone 5088 50.27% &Liver 332 3.28% &Heart 119 1.18% &Lung 8 0.08% &Pancreas 245 2.42% Non-kidney Transplant (Liver, Heart, Lung, or Pancreas) 4329 42.77% TXP: Transplant, HD: Hemodialysis.

136 Background: The ECOG performance status (PS) is a critical measure for evaluating functional capacity and determining clinical trial eligibility in patients with advanced prostate cancer. We aim to assess the capability of large language models (LLMs) to accurately infer ECOG PS from unstructured oncology notes. Methods: This retrospective study included patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177–PSMA-617 ( 177 Lu) at the Mayo Clinic (2022-2023). Baseline ECOG PS scores were manually curated by a trained clinician from clinical notes recorded within four weeks prior to 177 Lu initiation. Structured zero-shot prompts were then used to prompt GPT-4 to infer ECOG PS scores from unstructured oncology notes. Total dataset was randomly sampled to prompt development (20%) and held-out test set (80%). Three experimental setups were employed to assess model performance: (i) utilizing unmasked clinical notes, (ii) clinical notes with only numerical ECOG PS scores masked while retaining narrative descriptive/assessment by oncologist of ECOG score, and (iii) clinical notes with both numerical scores and narrative ECOG descriptors masked. Final performance was assessed using evaluation metrics (precision, recall, F1 score) on the held-out test set. Results: A total of 240 patients (n: 50 prompt development; n: 190 test set) were included in the analysis. The median age was 70 (IQR: 66-76); a majority of patients were White (n: 229; 95%) and non-Hispanic (n: 233; 97%). The most prevalent ECOG PS score was 0 (n: 140; 58%), followed by 1 (n: 88; 37%), and 2 (n: 12; 5%). The performance was numerically higher when using unmasked notes (weighted average precision: 0.89; recall: 0.89; F1: 0.89), compared to using notes with masked scores only (weighted average precision: 0.76; recall: 0.79; F1: 0.75) and notes with both scores and narrative masked (weighted average precision: 0.57; recall: 0.53; F1: 0.48). Metrics by each ECOG PS score is outlined (Table). Conclusions: Large language models demonstrate significant potential in precisely extracting ECOG performance status from unstructured oncology notes, offering valuable support for treatment decision-making and clinical trial enrollment. However, model performance declines as reliance on implicit reporting within clinical notes increases. Future efforts focusing on prediction of ECOG using a series of notes over time will be the next step. ECOG Unmasked oncology notes ECOG Score masked only ECOG Score + ECOG narrative marked Precision Recall F1 Score Precision Recall F1 Score Precision Recall F1 Score 0 0.89 0.92 0.91 0.75 0.93 0.83 0.59 0.74 0.66 1 0.88 0.86 0.87 0.76 0.74 0.75 0.19 0.47 0.27 2 1.00 0.82 0.90 0.78 0.33 0.47 0.78 0.16 0.26

132 Background: Distant metastasis at the time of prostate cancer (PCa) diagnosis is associated with increased morbidity and mortality. This study aimed to assess the impact of sociodemographic characteristics on distant metastasis at the time of PCa diagnosis. Methods: The Surveillance Epidemiology and End Results (SEER) database (2000-2021), including PCa patients from 17 registries, was queried. Patients with late-stage diagnosis (LSD) were defined as those who were initially diagnosed with stage IV disease, indicating distant metastasis. Sociodemographic predictors included race, ethnicity, age, marital status, residential status, and median household income. Multicollinearity was assessed using variance inflation factors (VIF). Univariable logistic regression was performed to identify significant predictors of LSD, which were further analyzed in multivariable logistic regression using a maximum likelihood estimation approach. Odds ratios with 95% confidence intervals (CI) were computed with a p-value of <0.05 indicating a statistically significant association. Results: Of the 1,089,736 PCa patients diagnosed, 64,983 (6%) had an LSD. The majority were white (80%), non-Hispanic/Latino (HL) (91%), aged ≥65 years (60%), married (75%), residents in metropolitan areas (88%), and had an annual house income of ≥$70,000 (70%). Multivariable logistic regression identified Black (OR: 1.24; 95%CI: 1.22-1.27), Asian or Pacific Islander (1.35; 1.30-1.40), and American Indian/Alaska Native (1.70; 1.53-1.89) to have higher odds of LSD compared to White patients (Table). In addition, HL ethnicity compared to non-HL (OR: 1.45; 95% CI: 1.42-1.49), age ≥65 compared to <65 (1.68; 1.65-1.71), unmarried status compared to married (1.88; 1.85-1.91), residency in non-metropolitan areas compared to metropolitan (1.10; 1.07-1.12), and household income <$70,000 compared to ≥$70,000 (1.03; 1.01-1.05) had a significant association with LSD. Conclusions: Older, non-White (Black, Asian/Pacific Islander, American Indian/Alaska Native), Hispanic/Latino, unmarried men, residents of non-metropolitan areas, or those with lower annual household incomes have higher odds of late-stage diagnosis. Interventions targeting early detection in these at-risk groups may improve prostate cancer outcomes in the US. Variable Odds Ratio (95% CI) p-value Race (Black vs White) 1.24 (1.22-1.27) <0.01 Race (Asian or Pacific Islander vs White) 1.35 (1.31-1.40) <0.01 Race (American Indian/Alaska Native vs White) 1.70 (1.53-1.89) <0.01 Ethnicity (Hispanic/Latino vs non-/Hispanic/Latino) 1.45 (1.42-1.49) <0.01 Age (≥65 vs <65) 1.68 (1.65-1.71) <0.01 Marital status (unmarried vs married) 1.88 (1.85-1.91) <0.01 Residence status (non-metropolitan vs metropolitan) 1.10 (1.07-1.12) <0.01 Household income (<$70,000 vs ≥$70,000) 1.03 (1.01-1.05) <0.01