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Increasing rice yield with low ammonia volatilization by combined application of controlled-release blended fertilizer and densification

Controlled-release blended fertilizer (CRBF) and densification can increase rice yield and nitrogen (N) efficiency. However, the effects of CRBF combined with densification on rice yield, N absorption, economic benefits of fertilization, and ammonia volatilization loss remain unclear. A 2-year field experiment was conducted using five treatments: no N (control, CK), conventional N application (farmer’s fertilization practice, FFP), optimal N application (OPT), single basal application of CRBF (CRBF), and CRBF combined with densification (CRFDP). Moreover, rice yield, N absorption and use efficiency, economic benefit, and ammonia volatilization loss were evaluated. CRBF and CRFDP significantly increased rice dry matter, N use efficiency by 11.6%–30.5% and 90.2%–160.0%, finally increased the yield by 33.3% and 26.1% in 2021 and 2022, respectively. Compared with FFP, CRFDP with 16.7% reduction of N input significantly increased yield by 33.3% and 26.1% and economic benefit by 46.9% and 38.3% in 2021 and 2022, respectively. Compared with CRBF, CRFDP increased the total yield by 2.7% and 15.2%, economic benefit by 3.5% and 7.6%, and N absorption efficiency by 10% and 8.3% in 2021 and 2022, respectively. Compared with FFP, CRFDP reduced ammonia volatilization intensity by 62.5% and 60.8%, cumulative ammonia volatilization loss by 46.3% and 50.3% and also lowered NH4+-N of surface water by 69.0%–93.8% and 57.8%–89.7% in 2021 and 2022, respectively. The combination of CRBF and densification could improve the rice yield, economic benefit, and N use efficiency and reduce ammonia volatilization. These results might provide data and theoretical support for the high yield of rice and a new environmentally friendly and resource-efficient model of rice cultivation.

Nutrition regulates reproductive senescence and terminal investment across the reproductive cycle of a long-lived mammal

Renal cell carcinoma in kidney transplant recipients receiving immunosuppression: A 55-year retrospective single-center study.

599 Background: Immunosuppression, the key post-transplant therapy to prevent organ rejection, is associated with an increased cancer risk. Kidney transplantation is the most frequent solid organ transplant, with renal cell carcinoma (RCC) being the most common urologic cancer in kidney transplant recipients (KTR). While numerous retrospective studies address RCC onset in KTR, they often have limitations, including small sample size, case series design, and lack of annotation regarding pathological features and immunosuppressive regimens adopted. Methods: We retrospectively evaluated 2,571 KTR between 1969 and 2024 at Grande Ospedale Metropolitano Niguarda, Milan, Italy. The primary aim was to assess the incidence of RCC after kidney transplantation. Also, we examined pathological features, including tumor histology, grade, stage, and site (native kidney or graft). Time from transplantation to RCC diagnosis and immunosuppressive regimens were assessed. Overall survival (OS) was evaluated using Kaplan-Meier estimates and Cox proportional hazards model. Results: RCC was diagnosed in 44 KTR, with an incidence of 1.7% (44/2,571, 95%CI 1.2-2.2). Median age at transplant was 48 years (IQR 38-57), with a median time from transplantation to RCC diagnosis of 9 years (IQR 3-18). RCC was diagnosed mostly in males (34/44, 77.3%) and in native kidney (33/44, 75%). Most cases were localized (42/44 pT1-T2, 95.5%), and all received definitive treatment including surgery (41/42, 97.6%) or radiofrequency (1/42, 2.4%). Stage IV at diagnosis was infrequent (2/44, 4.5%). With a median follow-up time of 7 years (IQR 2-10), RCC relapse after definitive treatment was rare (1/42, 2.4%). Bilateral or multiple tumors were observed in 3/44 patients (6.8%), with papillary histology (pRCC) as the most common subtype (24/47, 51.1%). Most KTR received triple immunosuppressive regimens, typically including steroids (90%), calcineurin inhibitors (86.4%), and mycophenolate (75%). There was no significant difference in clinical-pathological characteristics between patients with clear cell carcinoma (ccRCC) or pRCC. Median OS was 28 years (95%CI 23-NR) after transplantation and 10 years (95%CI 8-NR) after RCC diagnosis. Conclusions: This is to our knowledge the largest Italian monocentric case series of RCC arising in KTR. We observed a RCC incidence of 1.7% in this KTR population. The predominance of pRCC in this setting (51%) aligns with findings from previous studies with a higher frequency in KTR compared to the expected proportion in the general population (~10-15%). Despite a generally favorable prognosis, the low incidence of advanced-stage disease at diagnosis underscores the importance of early detection and vigilant surveillance in this high-risk population of KTR.

The impact of the Area Deprivation Index on immunotherapy outcomes in metastatic renal cell carcinoma (mRCC).

445 Background: The treatment landscape of mRCC has evolved in recent years with the advent of immune-checkpoint inhibitors (ICIs). The Area Deprivation Index (ADI) measures social determinants of health geographically, ranking neighborhoods by socioeconomic disadvantage. However, there are limited data on ICIs outcomes in relation to ADI. We investigated the association between ADI and clinical outcomes of ICI in mRCC. Methods: We conducted a retrospective analysis of 560 mRCC patients (pts) treated at our institution from 2013 to 2024. Eligibility included metastatic disease and ICI treatment at any line. Baseline characteristics and treatment outcomes were obtained from chart review. The ADI scores were calculated by entering the pts addresses at the time of starting ICI into the Neighborhood Atlas. The results were categorized into four quartiles (1st:1-25, 2nd: 26-50, 3rd: 51-75, 4th: 76-100), with higher scores indicating greater deprivation. Overall survival (OS) and progression-free survival (PFS) were calculated from the start of ICI by the Kaplan-Meier method. Immune-related toxicity was assessed across ADI groups. Univariate and multivariate analyses were performed to assess the impact of ADI on survival outcomes, controlling for confounding variables. Results: Our analysis included 287 eligible mRCC pts. Most pts were male (n=208, 72%) with a median age at ICI start of 63 years. Primary histology was clear cell in 238 pts (83%). Pts were 79% White, 13% Black, and 7% other races. Most pts received ICI in the first line (65%) and in combinations (71%). Based on ADI quartiles, 46.3% were in the 1st, 32.4% in the 2nd, 15.3% in the 3rd, and 6% in the 4th quartile. Survival analyses revealed that pts in the highest ADI quartile (4th) had significantly shorter OS (p=0.01) and PFS (p=0.03) compared to those from areas with lower ADI scores. Multivariate analysis confirmed shorter OS in the highest ADI quartile (HR 2.39 [1.32, 4.31], p=0.004). No significant differences in immune-related toxicity rates were observed. Univariate analysis of the continuous ADI values revealed a correlation of higher scores with shorter OS (HR 1.24 [95% CI: 1.06-1.46] p=0.008) and PFS (HR 1.17 [95% CI: 1.02-1.35] p=0.03). Conclusions: Despite landmark improvements in survival outcomes with ICIs in mRCC, pts in deprived areas continue to experience poorer outcomes, highlighting the need for targeted interventions to enhance access to care and to better understand how neighborhood deprivation impacts overall health both prior to diagnosis and over the course of care. Further pan-cancer studies are essential to validate these findings.

Impact of PSA nadir on long-term survival in metastatic hormone-sensitive prostate cancer: Final 10-year analysis of the ECOG-ACRIN E3805 CHAARTED trial.

167 Background: Addition of docetaxel (D) to ADT has demonstrated improved overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). In this post hoc OS analysis of the CHAARTED trial (NCT00309985), we report 10-year OS and cause of death (COD) by baseline clinical factors, PSA nadir at 6 months in mHSPC patients treated with ADT +/- D. Methods: An updated survival sweep was conducted in July 2024. Patients were prospectively identified by the state of metastatic disease (metachronous/prior local therapy vs. synchronous/no prior local therapy) and low volume (LV) vs. high volume (HV; visceral and/or ≥4 bone metastases with one lesion beyond the vertebral bodies or pelvis) disease. OS defined as time from 6 mos post randomization to death was calculated using the Kaplan-Meier method and compared between PSA nadir (<0.2 vs. ≥0.2) groups using the log rank test. Results: A total of 334 patients achieved PSA nadir of <0.2 at any timepoint with a median time to PSA nadir of 4.8 months. At 6 months, PSA nadir <0.2 was seen in 204 (26.8%) patients. Patients with PSA nadir <0.2 had significantly better median OS in both ADT + D (100.3 vs. 45.4 mos; P<0.0001; Table) and ADT (116.8 vs. 31.8 mos; P<0.0001) arms. This prognostic impact was significant across prespecified prognostic subgroups. Of the 101 patients who achieved a PSA of < 0.2 at 6 mos, the COD was ‘prostate cancer’ in 58.4% (n=59), ‘other’ in 14.9% with 26.7% being unknown. Of the unknown/missing (n=27), 10 patients died without a record of having progression. In the PSA nadir ≥0.2 group, the reported COD was ‘prostate cancer’ in 78.2% with 6.5% being ‘other' and 15.4% being unknown/missing. Conclusions: Compared with patients with PSA ≥0.2, PSA nadir of <0.2 at 6 months was associated with less prostate cancer deaths and more than doubling of the median OS with approximately 50% of patients alive at 8 years across treatment and all prespecified prognostic groups except de novo high volume treated with ADT alone. Clinical trial information: NCT00309985 . Outcomes by PSA nadir at 6 months in overall population and pre-specified subgroups. ADT+ D ADT # Death/N Median OS (95% CI; months) p-value # Death/N Median OS (95% CI; months) p-value Overall 6-month PSA <0.2 66/127 100.3 (70.4, NA) <0.0001 35/77 116.8 (87.3, 141.5) <0.0001 6-month PSA ≥0.2 203/256 45.4 (39.2, 51.6) 246/301 31.8 (26.3, 38.1) Denovo HV6-month PSA <0.2 20/39 93.5 (45.9, NA) 0.0001 7/11 74.7 (37.4, NA) 0.007 6-month PSA ≥0.2 135/166 39.5 (32.8, 48.5) 162/183 26.4 (23.5, 32.0) Metach HV6-month PSA <0.2 12/23 105.7 (61.4, NA) 0.0009 8/15 87.3 (47.4, NA) 0.0002 6-month PSA ≥0.2 22/25 43.2 (23.5, 66.0) 25/26 22.1 (13.9, 39.4) Metach LV6-month PSA <0.2 18/34 101.5 (58.6, NA) 0.04 11/38 123.4 (123.4,141.5) 0.003 6-month PSA ≥0.2 17/21 63.6 (49.7, 99.3) 14/26 48.9 (25.6, NA)

Characterization of genitourinary drug approvals by the FDA, 2020-2024.

872 Background: There were 255 cancer drug approvals by the US Food and Drug Administration (FDA) between January 2020 and October 2024. Although genitourinary (GU) cancers (prostate, urothelial, renal and testicular) compromise some of the most prevalent malignancies, it is unclear how many of these drug approvals were intended for treatment of genitourinary cancers. Methods: Using the list of FDA cancer drug approvals, we identified approvals for GU cancer indications between January 2020 and October 2024. We collected data on tumor type, line of treatment, control arm, primary endpoint(s) as studied in the corresponding clinical trial, and phase of clinical trial. Results: We identified a total of total of 26 drug approvals for GU cancer indications (10.2%) among the total 255 drug approvals for all cancer types. Among these approvals, 12 were for urothelial, 9 for prostate, and 5 for renal. There was variation in the line of setting for each approval’s intended use as shown in the table. No cancer drug approvals were for testicular, penile or adrenal cancer. Most trials were phase III (n = 20), followed by phase II (n = 4) and then one each for phase IB/II and II/III. Overall survival was the most common endpoint (n = 10), followed by response rate and duration of response (n = 7), radiographic progression-free survival (n = 5), disease-free survival (n = 2), and one each for castration rate and metastasis-free survival. Conclusions: Drug approvals for GU cancers compromised approximately 10% of drug approvals by the FDA over the past five years. While OS continues to be the most commonly used endpoint in clinical trials, response rate and duration of response are commonly employed in BCG-refractory non-muscle invasive bladder cancer trials and radiographic progression-free survival in prostate cancer trials. Given the high incidence and mortality from GU cancers, continued drug development is warranted. Intended setting of use for genitourinary cancer drug approvals by tumor type, 2020-2024. Tumor Type Number Indication Urothelial 12 First line (n = 3), adjuvant (n = 1), maintenance (n = 1), BCG-refractory/UTUC (n = 4), second- or later-line (n = 3) Prostate 9 Hormone-sensitive (n = 2), hormone-resistant (n = 1), biochemical recurrence (n = 1), BRCA/HRD mutated (n =5) Renal 5 First-line (n = 2), adjuvant (n = 1), second- or later-line (n = 2) Testicular 0 No applicable Penile 0 Not applicable Adrenal 0 Not applicable 26

Modelling the impact of behavioural interventions during pandemics: A systematic review

Background Many studies examined the impact of behavioural interventions on COVID-19 outcomes. We conducted a systematic review to gain insight into transmission models, following PRISMA 2020 guidelines. We included peer-reviewed studies published in English until December 31, 2022, focusing on human subjects, modelling, and examining behavioural interventions during COVID-19 using real data across diverse geographical regions. Methods We searched seven databases. We used descriptive analysis, network analysis for textual synthesis, and regression analysis to identify the relationship between the basic reproduction number R 0 and various characteristics. From 30, 114 articles gathered, 15, 781 met the inclusion criteria. After deduplication, 7, 616 articles remained. The titles and abstracts screening reduced these to 1, 764 articles. Full-text screening reduced this to 270, and risk-of-bias assessment narrowed it to 245 articles. We employed combined criteria for risk of bias assessment, incorporating domains from ROBINS-I and principles for modeling. Results Primary outcomes focused on R 0 , COVID-19 cases, and transmission rates. The average R 0 was 3.184. The vast majority of studies (90.3%) used compartmental models, particularly SEIR models. Social distancing, mask-wearing, and lockdowns were frequently analyzed interventions. Early and strict implementation of these interventions significantly reduced transmission rates. Risk of bias assessment revealed that 62.6% of studies were of low risk, 24.1% moderate, and 9.3% high risks. Common issues included transparency, attrition bias, and confounding factors. Conclusions This comprehensive review highlights the importance of behavioural interventions in reducing COVID-19 transmission and areas for improving future research transparency and robustness. Our risk of bias criteria offers an important framework for future systematic reviews in modeling studies of interventions. We recommend that future studies enhance transparency in reporting and address common biases such as attrition and confounding.

Author Correction: Validation of a blood biomarker panel for machine learning-based radiation biodosimetry in juvenile and adult C57BL/6 mice

Investigation of ferroptosis and mTOR signaling in chromophobe renal cell carcinoma (ChRCC).

583 Background: ChRCC is a rare form of kidney cancer that has shown limited response to immune checkpoint inhibitors currently used as the standard-of-care for other RCC histologies. mTOR inhibition is a therapeutic strategy for advanced ChRCC, but the mechanistic basis for response remains poorly understood. We investigated clinical responses to mTOR inhibitors in patients with ChRCC and explored the underlying mechanism of therapeutic response at single-cell resolution. Methods: Clinical data from the International Metastatic RCC Database Consortium (IMDC) was used to evaluate survival outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with metastatic ChRCC compared to metastatic clear cell RCC (mccRCC) treated with first-line mTOR inhibitors. To uncover the mechanisms underlying ChRCC’s clinical response and identify future therapeutic targets, we compared gene expression in ChRCC tumor cells against their cell-of-origin via scRNA-seq analysis. Epithelial cells from matched normal kidney samples were clustered and annotated into distinct known cellular types of the healthy human kidney. A logistic regression model (Young M.D. et al., 2018) was trained on normal epithelial clusters, using a set of 74 marker genes. The model was tested on ChRCC tumors to identify their cellular origin by finding the highest predicted probabilities of similarity between normal epithelial cellular types and tumor cells. Validation analysis was conducted using a separate training set (KPMP Atlas). Differential gene expression and pathway analyses between ChRCC and its cell-of-origin were then conducted. Results: Patients with metastatic ChRCC exhibited higher overall survival (OS) compared to those with metastatic clear cell RCC when treated with first-line mTOR inhibitors (median OS: 41.3 months [95% CI: 14.4-NR] vs. 13.4 months [95% CI: 10.9-15.3], respectively). After quality control, 7,425 cells from ChRCC tumors and 784 epithelial cells from adjacent normal kidney tissue were isolated for scRNA-seq analysis. Normal epithelial cells were classified into proximal tubule, loop of Henle – distal tubule, principal cells, α-intercalated cells (ICA), and β-intercalated cells (ICB). The ChRCC tumor cells showed the highest similarity to ICA cells (0.60 probability), which was confirmed in the validation analysis. Among the most upregulated genes in ChRCC compared to ICA were NUPR1, FTL, and FTH1, all associated with the inhibition of ferroptosis. The top enriched pathways included NFE2L2 signaling, ferroptosis, and mTORC1 signaling. Conclusions: Metastatic ChRCC patients demonstrate improved overall survival compared to mccRCC patients when treated with mTOR inhibitors as first-line therapy. ChRCC appears to originate from ICA cells of the normal kidney. Potential therapeutic targets in ChRCC include ferroptosis and mTOR signaling pathways.

Prospective analysis of AR-V7 expression in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) sequentially treated with docetaxel and enzalutamide.

250 Background: Androgen receptor splice variant 7 (AR-V7) has been associated with poor outcomes in mCRPC patients treated with androgen receptor pathway inhibitors (ARPI). However, its predictive value is still not clear. Methods: We conducted a prospective single-arm trial to evaluate the role of AR-V7 as a potential predictive biomarker for ARPI treatment. Patients were initially treated IV with docetaxel 75 mg/m2. Enzalutamide 160 mg daily PO was started upon progression. Blood samples were harvested before docetaxel (C1), before enzalutamide (C2), and at the time of progression on enzalutamide (C3). Outcomes analyzed included PSA50 response (decline of 50% or more from baseline), PSA Progression-free Survival (PFS), and Overall Survival (OS) from the start of treatment. AR-V7 expression in circulating tumor cells was detected using AdnaTest Prostate Cancer Detect kit (Qiagen). Results: From October 2019 to July 2021, 30 patients were included. AR-V7 expression was detected in 40% of patients at C1, 46% at C2, and 74% at C3. All four patients who became AR-V7 positive at C2 responded to enzalutamide. The PSA50 to docetaxel was 33.3%. There was no significant difference in PSA50 between AR-V7pos and AR-V7neg patients at C1 (Table). The PSA50 to enzalutamide was 79.3%. Similarly, there was no significant difference in PSA50 between AR-V7pos and AR-V7neg at C2 (Table). The median PFS to docetaxel and enzalutamide were 6.0 mo and 15.0 mo, respectively. There was no significant difference in PFS to docetaxel between AR-V7pos and AR-V7neg patients at C1. PFS on enzalutamide was 9.0 mo for AR-V7pos and 20.0 mo for AR-V7neg patients at C2, but the difference was not statistically significant (Table). The median PFS to the sequential treatment and OS were 23.0 mo and 30.0 mo, respectively. AR-V7pos patients at C1 had shorter PFS to sequential treatment and shorter OS (Table). Conclusions: AR-V7 expression was not associated with response to docetaxel and enzalutamide but with shorter PFS and OS to sequential treatment. AR-V7 expression may be considered a prognostic, but not predictive, biomarker in mCRPC patients. Clinical trial information: NCT03700099 . AR-V7 status at C1 AR-V7 pos AR-V7 neg OR/HR (IC95%) p-value PSA50 to Docetaxel 33.3% 35.3% OR 1.90 (0.23-5.20) >0.999 * PFS on Docetaxel 5.0 mo 6.0 mo HR 1.73 (0.80-3.73) 0.164 # PFS on Doce + Enza 13.0 mo 28.0 mo HR 2.74 (1.16-6.50) 0.022 # OS 20.0 mo 41.0 mo HR 3.28 (1.30-8.27) 0.012 # AR-V7 status at C2 AR-V7 pos AR-V7 neg OR/HR (IC95%) p-value PSA50 to Enzalutamide 76.9% 80% OR 1.20 (0.20-7.31) >0.999 * PFS on Enzalutamide 9.0 mo 20.0 mo HR 1.95 (0.82-4.64) 0.131 # OR=odds ratio, HR=hazard ratio; * Fisher's exact test; # Kaplan Meier and Log-rank.

The impact of micropapillary histology and clinical staging on overall survival in bladder cancer: A retrospective analysis.

744 Background: Micropapillary variant bladder cancer (MPC) is a rare subtype of urothelial carcinoma, representing 0.01–2.2% of cases, with a higher stage at diagnosis and increased metastatic potential. The prognostic role of MPC remains uncertain, and previous studies have been limited by small cohort sizes, with only a few larges studies. This study analyzed the prognostic impact of MPC on clinical stage and survival outcomes in the largest single-institution cohort of patients with MPC who underwent radical cystectomy (RC). Methods: This retrospective study included 130 patients who underwent RC at Memorial Sloan Kettering Cancer Center for MPC between June 21, 1995, and April 14, 2023. Data included demographic, histologic, and clinical variables, as well as overall survival (OS) outcomes. Cystectomy specimens were reviewed by genitourinary pathologists to determine the proportion of the MPC component (MPC%) in each tumor. For OS comparison, a separate cohort of 430 patients with urothelial carcinoma not otherwise specified (UC NOS) who also underwent RC was used. Patients with MPC were further stratified by stage at diagnostic transurethral resection of bladder tumor (TURBT) as either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). Additional stratifications included MPC% ( < 50% vs. ≥50%, < 20% vs. > 80%) and receipt of neoadjuvant chemotherapy (NAC). Results: MPC was associated with a significantly shorter OS compared to UC NOS patients (p = 0.011). The MPC cohort had a mean OS of 83.8 months (95% CI: 62.2–105.4) and a median OS of 36.8 months (95% CI: 22.3–51.3), whereas the UC NOS cohort had a mean OS of 72.1 months (95% CI: 66.6–77.6) and a median OS of 84.4 months (95% CI: 64.5–104.2). Within the MPC cohort, patients with MIBC at initial TURBT had significantly worse OS compared to those with NMIBC (p = 0.0005). MPC% did not impact OS, with no differences between patients with < 50% versus ≥50% MPC (p = 0.59) or < 20% versus > 80% MPC (p = 0.57). Additionally, NAC did not affect OS within the MPC cohort (p = 0.055). N stage at cystectomy (N0 vs. N1+) was also not predictive of OS (p = 0.16). Conclusions: The presence of MPC, regardless of its proportion or the use of NAC, predicts poor outcomes. Clinical stage—particularly the presence of muscle invasion—remains the key predictor of survival. These findings emphasize the importance of clinical staging in guiding treatment decisions and prognostic assessments in the management of this disease.

Incidence and mortality trends in genitourinary cancer in Southeast Asia from 1990-2021.

619 Background: The global burden of genitourinary (GU) cancers has been increasing due to aging populations and advancements in technology. However, little is known about the burden of GU cancers specific to Southeast Asia (SEA), a diverse region of over 690 million people. This study presents the most updated trends in incidence and mortality of the bladder, kidney, prostate, and testicle cancers across SEA from 1990 to 2021. Methods: Data were extracted from the Global Burden of Disease (GBD) 2021 database to analyze the incidence, deaths, and age-standardized rates (ASR) by sex and age for four major GU cancers in Brunei, Cambodia, Timor-Leste, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam from 1990 to 2021. Results: From 1990 to 2021, SEA countries had an increase in overall GU cancer incidence (16,947 to 74,556) and mortality (20,500 to 61,113) for all ages. Bladder cancer showed the greatest rise in incidence (4,334 to 15,783) and deaths (8,586 to 24,375) for both sexes, while prostate cancer had the largest absolute increase in male incidence (8,431 to 42,362) and mortality (6,850 to 23,764). For bladder cancer, Thailand had the highest ASIR in 2021 for males, and Brunei for females. From 1990 to 2021, ASIR rose in Vietnam but decreased in Singapore for males, while rising in Malaysia for females. The highest ASMR in 2021 was in Malaysia for males and Brunei for females. From 1990 to 2021, ASMR declined in Singapore for males and in Singapore, Thailand, and Myanmar for females. For kidney cancer, Brunei had the highest ASIR and ASMR in 2021 for both sexes. From 1990 to 2021, ASIR rose in all countries except Timor-Leste, Myanmar, and Laos for males, and increased in Malaysia, Philippines, Indonesia, Singapore, Thailand, and Vietnam for females. ASMR rose in Indonesia, Thailand, Vietnam, and Philippines in males, and in Indonesia and Vietnam for females. For prostate cancer, Singapore had the highest ASIR in 2021, with ASIR increasing in all countries except Laos from 1990 to 2021. ASMR was highest in the Philippines in 2021. From 1990 to 2021, ASMR rose in Cambodia and Indonesia. For testicular cancer, Singapore had the highest ASIR in 2021. From 1990 to 2021, ASIR rose in all countries but Brunei and Philippines. ASMR was highest in Malaysia in 2021 and remained stable throughout the region from 1990 to 2021. Conclusions: The burden of GU cancers in SEA has significantly increased from 1990 to 2021, with bladder and prostate cancers showing the largest rises in incidence and deaths. Brunei consistently exhibited the highest ASIR and ASMR for kidney and bladder cancers. For prostate and testicular cancer, Singapore had the highest ASIR while ASMR was highest in the Philippines for prostate and Malaysia for testicular cancer. These findings highlight the urgent need for enhanced resource allocation and targeted interventions to address the growing GU cancer burden and disparities in the region.

Gaps, challenges and opportunities towards achieving the 95-95-95 targets in Cameroon: A systematic review and meta-analysis protocol

Background Given HIV elimination by 2030, the World Health Organization and the United Nations’ Programme on HIV/AIDS (UNAIDS) have set three programmatic goals that all countries should have achieved before 2025; 95% of people living with HIV should know their status (target-1); 95% of people who know their status should be linked to treatment (target-2); and 95% of people on treatment should achieve viral load suppression (i.e. VL<1000 copies/ml; target-3). Despite considerable global progress over the past decade, many low-middle-income countries are still below the expected targets. This review protocol aims to provide a standardized document for in-depth analysis of the strengths, weaknesses, opportunities and threats (SWOT) towards achieving these programmatic targets in Cameroon. Methods This systematic review will include randomized and non-randomized trials, cohorts, case-controls, cross-sectional studies, case reports and governmental notices addressing the achievements, the gaps, the challenges and the opportunities towards the 95-95-95 targets in Cameroon. The search will consider studies from 2017 to 2024, retrieved from PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, online African journals, and Cumulative Index to Nursing and Allied Health Literature. We will include studies reporting HIV diagnosis, HIV link to treatment or HIV viral suppression in Cameroon. Results will be stratified according to time, age-group (adults’ vs adolescents/children) and geographic locations. Primary outcomes will be “estimates on 95-95-95 programmatic goals at the national level”. Secondary outcomes will consist of the SWOT analysis towards achieving these programmatic targets. A random-effects model will be used to calculate pooled prevalence if data permits. Conclusions This systematic review and meta-analysis protocol will guide global estimation on the achievement of the 95-95-95 targets as well as the stakes and challenges within the Cameroonian setting. Final evidence from the systematic review will allow identification of the gaps and measures to be taken to fasten our move towards the 95-95-95 in Cameroon by 2025. Systematic review registration Systematic review registration: CRD42024502755.

Bioinformatics Analysis of coagulation-related genes in lung adenocarcinoma: unveiling prognostic indicators and treatment pathways

Clinical outcomes of lutetium-177-vipivotide tetraxetan in men with metastatic castration-resistant prostate cancer at a single academic center.

84 Background: Lutetium-177-vipivotide tetraxetan ( 177 Lu) was approved in 2022 for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with prior androgen receptor signaling inhibition (ARSI) and a taxane. The impact of 177 Lu in a non-trial setting is limited. Methods: We retrospectively reviewed records of mCRPC pts who received ≥1 dose of 177 Lu at The Ohio State University from 3/2022-3/2024. Demographics, tumor histology, metastasis sites (mets), treatment (Tx) history, standardized uptake value max (SUVm), and prostate-specific antigen (PSA), at baseline (BL) and post-Tx were collected. SUVm was defined as the highest SUV from a single lesion. Outcomes were PSA response, PSA50, radiographic progression-free (rPFS) by PCWG3, and overall survival (OS). Descriptive statistics, Mann-Whitney, Chi-square, and Cox regression model were used to assess impact. Results: A total of 152 pts were included with a median follow-up of 9 months (0.1-23 m). The median age was 70 years (46-92 y), with 39% having de novo metastatic disease, and 61% had Gleason grade group ≥4. The common mets were bone (91%), lymph node (68%), and visceral (34% with 17% liver and 8% lung). The majority received prior taxanes and ARSI, and 20% radium-223. The median lines of prior Tx was 5.The median BL PSA was 56.3 ng/mL, and the median BL SUVm was 30.4. Post-Tx, 64% showed a PSA response, and 46% achieved PSA50. Among the pts with available imaging, 17% had partial response, 12% stable disease, and 48% disease progression.Tx was discontinued in 62% for:radiographic progression (66%), PSA-only progression (7%), clinical decline (24%), and toxicity (3%). At the data cutoff, mortality was 50%. Median PFS and OS was 6.7 m, and 12.2 m respectively. BL SUVm was associated with improved PSA50 (p=0.01), rPFS (p<0.01), and OS (p=0.01), and liver mets associated with worse OS (p<0.01). Conclusions: In this retrospective study of 177 Lu, we see similar PSA and PSA50 responses to reported trials. However, PFS was shorter, and mortality was higher, likely related to the use of 177 Lu in heavily treated pts with few remaining options. Optimizing biomarkers to predict Tx benefit and resistance are needed.

<i>g</i> -Rate–based machine learning model to predict overall survival (OS) in patients with metastatic prostate cancer (mPC) while on treatment.

242 Background: Dynamic biomarkers to predict OS while a pt is on treatment are unavailable in mPC. We have developed g -rate method which can estimate tumor growth ( g ) and decay ( d ) rates using PSA values. This has been validated to show a robust inverse correlation with OS using 13 clinical trials and real-world data from the US Veterans. We now explore the g -rate method in developing a multimodal machine learning (ML/AI) tool to serve as a dynamic biomarker predicting OS while a pt is on treatment. Methods: We have created a comprehensive VA database with more than 20,000 pts to assess drug efficacy in mPC. g and d rates are calculated using PSA values while on treatment via the TUMGr package for R. All available variables such as age at the start of treatment, race, treatment setting (rural vs urban), gleason score, charleson comorbidity index (CCI), hormone sensitivity, line of treatment, serial PSA, and g -rate while on treatment. The histogram-based gradient boosting tree ML algorithm is used to build the classifier. This algorithm is optimized to handle large data (records &gt; 10,000). Sample reweighting is used to account for data imbalance by adjusting weights inversely proportional to class frequencies in the training data. Permutation importance is used to assess the significance of features in the resulting model. A binary classifier is used to predict the survival status. Shapley additive explanations (SHAP) were used to evaluate the contribution of individual features. Results: We utilized data from 25641 treatment records from 22958 unique pts; 20475 records were used for training and 5166 were used for testing ML algorithm. We identified 16 features, including demographic, CCI, baseline PSA, baseline CBC, and PSA-based g-rate for the model. The resulting model yielded an accuracy of 77%, a precision of 89.7%, a sensitivity/recall of 79%, a specificity of 73%, and an F1-score of 84%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.83. The classification results were statistically significant (p&lt;10 -6 ).The mean absolute SHAP values revealed that starting PSA and g -rate were 2 most influential features in predicting pt survival. The model showed concordant results amongst White, Black, Hawaiian, and American Indian races, but not for Asian pts (Table). Conclusions: g -rate-based ML/AI model can accurately, consistently and reliably predict pt survival while being treated for mPC across different races as soon as 3 months once the g -rate is calculated after starting treatment. Future incorporation of this model into clinical trials may identify opportunities for early intervention for those with poor prognoses. Race Records Accuracy AUC score Precision White 3520 0.78 0.83 0.9 Black 1387 0.76 0.83 0.9 Native Hawaiian 44 0.80 0.96 1 American Indian 27 0.85 0.93 0.9 Asian 20 0.65 0.69 0.7 Unknown 168 0.77 0.86 0.9 All 5166 0.77 0.83 0.9

Vasculo-immune modulatory effects of anti-VEGF therapy in metastatic clear cell renal cell carcinoma: The A-PREDICT trial.

572 Background: Anti-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors and checkpoint inhibitors (CPI) a standard-of-care treatment for clear cell renal cell carcinoma (ccRCC). We investigated the biology underpinning benefit of anti-VEGFR TKI in the phase II A-PREDICT trial (NCT01693822), evaluating pre- and post-treatment, fresh multiregion tumour biopsies in patients with metastatic ccRCC treated with first-line axitinib. Methods: We analysed 123 tumour samples from 52 patients, 28 with paired pre/post-treatment samples. Post-treatment samples included week-9, nephrectomy, and on-progression timepoints. ‘Responders’ had progression-free survival (PFS) ≥6 months (n=35), ‘non-responders’ with PFS &lt;6 months (n=17). We applied a custom Nanostring panel for gene expression analysis and multiplex immunofluorescence (mIF) for orthogonal validation. Wilcoxin test was used to analyze paired observations. Results: At baseline, angiogenesis scores were similar between responders and non-responders (p=0.22). Post-treatment, the angiogenesis, vascular sprouting, and endothelial cell proliferation signature scores were significantly decreased (p=0.023, 0.0034, &amp; 0.0082, respectively) in all patients, suggesting suppression of angiogenesis and neovascularisation irrespective of clinical outcomes. mIF in 3 patients (with PFS of 3, 5.6, &amp; 100 months) confirms widespread intratumoral vessel depletion. Immune deconvolution analysis shows total levels of T cells and CD8 + T cells were similar pre- and post-treatment, suggesting axitinib did not enhance immune cell trafficking. Rather, axitinib promoted increased levels of exhausted CD8 + T cells post-treatment (p=0.01). M2 tumour-associated macrophages increased post-treatment in responders (p=0.033) but not in non-responders (p=0.44). A minority of patients had durable (&gt;2 years) responses to axitinib (n=7/65, 6 with tissue for analysis). In these patients, we found higher levels of pre-treatment intratumoral cytotoxic immune cells (p=0.041) and NK cells (p=0.015) compared to patients with primary resistant disease. Conclusions: Axitinib suppressed angiogenesis and neovascularisation leading to intratumoral vessel depletion, and therapy response associates with features of an immunosuppressive TME. Baseline endogenous immune priming appears critical for durable response to anti-VEGF therapy. These data are relevant to understanding the clinical efficacy of combined anti-VEGF and CPI regimens. Clinical trial information: NCT01693822 .

The role of conventional imaging and piflufolastat F18 in newly diagnosed and recurrent prostate cancer patients: Preliminary observations from the PYLARIFY Registry.

41 Background: Next generation imaging modalities for the diagnosis and characterization of prostate cancer have seen increased utilization in the past several years. PSMA-PET imaging has seen particular promise as a more accurate modality compared to conventional (CT, skeletal scintigraphy and PET) imaging. Use of PSMA imaging can significantly improve how prostate cancer is staged and thus enhance the clinicians’ confidence in therapeutic decision making. Methods: The PYLARIFY Registry (NCT 05712473), conducted under SoNaR, a Specialty Networks Registry, is a US-based multi-center prospective 5 year observational study following patients receiving standard of care piflufolastat F18 imaging as part of their prostate cancer management. The registry includes newly diagnosed patients who have not yet initiated any treatment (Cohort 1) and patients with biochemical recurrence (Cohort 2). Demographics, all baseline imaging procedures and the frequency of each type of imaging for the first 100 enrolled patients were analyzed. We also explored time-to-PSMA for newly diagnosed patients who received conventional imaging as part of their staging assessment. The clinician confidence ratings that the piflufolastat F18 imaging had on treatment decision making were also evaluated. Results: The first 100 patients had a mean age of 71.0 (SD 9.1) and 80% had a Gleason Grade group of 2 or higher. At least 1 conventional imaging procedure prior to the piflufolastat F18 PET scan was performed on 10% of patients in Cohort 1 and 77% in Cohort 2. For Cohort 1 patients, piflufolastat F18 scans were preceded by a total of 4 imaging procedures, with an average of 1 conventional imaging procedure per patient prior to their piflufolastat F18 scan. Cohort 2 patients had a total of 95 imaging procedures with an average of 1.58 conventional imaging procedures per patient prior to their piflufolastat F18 scan. The 3 most utilized conventional imaging modalities in both cohorts of patients that received conventional imaging prior to piflufolastat F18 scans were CT (80%), and skeletal scintigraphy (72%) and PET (26%). The median difference in diagnostic journey length between Cohort 1 newly diagnosed patients having conventional imaging and those having only piflufolastat F18 was 28 additional days. Across both cohorts, clinicians rated improvement in treatment planning confidence following 96% of piflufolastat F18 scans. Conclusions: Piflufolastat F18 provides a high degree of confidence for prostate cancer patient management. A growing number of patients are being managed with piflufolastat F18 scans only. Many patients however still undergo lengthy and resource-intensive conventional imaging procedures prior to their piflufolastat F18 scan.

In vitro antibiofilm efficacy of ertapenem, tobramycin, and moxifloxacin against biofilms grown in a glass bead or CDC Biofilm Reactor®

Laboratory grown biofilms are used to simulate bacterial growth in diverse environmental conditions and screen the effectiveness of anti-biofilm therapies. Recently, we developed a glass bead biofilm reactor that utilizes low broth volume to provide high-throughput biofilm growth for testing and translation across the research continuum (e.g., benchtop assays to preclinical models). Bioburden per mm2 surface area of Staphylococcus aureus and Pseudomonas aeruginosa biofilms were comparable on beads and CDC Biofilm Reactor® coupons. In this study, we hypothesized that biofilms grown on beads would be more susceptible to ertapenem, moxifloxacin, and tobramycin than those grown on coupons. Results indicated a significant reduction in S. aureus bioburden on glass beads compared to glass coupons following treatment with ertapenem (p = 0.005) and tobramycin (p = 0.014). P. aeruginosa biofilms had smaller differences in antibiotic response between the two systems. There was a significantly greater reduction in bead P. aeruginosa biofilm than coupon when treated with tobramycin (p = 0.035). This work offered insight into how the bead biofilm reactor could be used as a tool for antibiotic screening and translation across the continuum of in vitro to in vivo systems that support development of antimicrobial technology.

Development of a wireless electroretinogram recording system

Abstract A novel device consisting of amplifiers, an analogue-digital converter, offset correction units, and a microcontroller with Bluetooth wireless functionality was fabricated. Electroretinography (ERG) recordings were captured in dark-adapted and light-adapted full-field flash stimulations in an anaesthetised animal model using the novel wireless system. Recordings were repeated using a standard ERG recording setup of the Espion E3 system for comparison. The electroretinogram signal a-wave and b-wave amplitudes, peak times, signal offset, potential drift, and power line noise were compared between the recording setups. Signals from the novel system were found to have similar waveforms to those recorded from the standard ERG setup. There were no significant differences in the a-wave amplitudes ( P &gt; 0.43), a-wave peak times ( P &gt; 0.61) and b-wave peak times ( P &gt; 0.55). The offset potential drift when using the novel system was significantly smaller than the reference system ( P &lt; 0.02). The novel system also showed stronger resilience against powerline noise interference, as evidenced by a statistically significant performance increase during recordings with substantial noise interference ( P &lt; 0.01). The on-source signal processing and wireless transmission can improve the quality of recorded ERG signals. Our study demonstrates a proof of concept for performing wireless ERG recordings, which enhance the performance by reducing noise and potential drift in the recorded signals.