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Effects of different high-intensity interval training modes of wattbike on anaerobic capacity in Chinese national alpine skiers

Changes in CTCAE v6: Effect on dose-escalation and dose-limiting toxicity with repeat analysis of recent clinical trials.

143 Background: Several therapeutic modalities for cancer have associated myelosuppression. Amongst changes in CTCAE v6, grade (Gr) 4 thrombocytopenia (plts) has been redefined as a platelet count <10,000/dL (< 25,000/dL in CTCAE v.5) and lymphopenia is limited to Gr 0-2 (previously Gr 0-4). Common definition of dose-limiting toxicity (DLT) includes Gr 3 non-hematologic toxicity or Gr 4 hematologic toxicity. Using newer grading to define DLT may result in higher recommended phase 2 dose (RP2D) in future trials. Methods: We retrospectively reviewed prospectively collected data of 208 patients from phase 1 trials of targeted radionuclide therapy and/or chemotherapy in patients with advanced cancer (NCT03276572, NCT03042468, NCT04576871, NCT04506567, NCT04886986, NCT02913196, NCT04946370, NCT00967577) and regraded according to CTCAE v.6 adverse events list. Results: Across 8 studies 17 DLTs were discovered per CTCAE v5. Among them 6 (35.3%) were confirmed cases of Gr 4 thrombocytopenia’s (TCP) and 1 Gr 4 TCP and anemia (5.9%) Other DLTs included 3 Gr 1, 3 Gr 2 and 2 Gr 3 thrombocytopenia delaying cycle 2/C3 for >3 weeks, 1 Gr 3 Hypertension and 1 Gr 3 hepatic failure. Among these none (n=7) of the Gr 4 TCP would have been deemed DLT using CTCAE v6 criteria, with a 41% reduction in observed DLTs. Hence, the RP2D may have been different had the trials been conducted using the new criteria of adverse events. Conclusions: Changes in grading by CTCAE may result in different administered dose or schedule of drugs with associated myelosuppression in the near future. Clinical trial information: NCT03276572 , NCT03042468 , NCT04576871 , NCT04506567 , NCT04886986 , NCT02913196 , NCT04946370 , NCT00967577 . List of DLT according to clinical trials. Trial Subject DLT Platelet count CTCAE v.5 grading CTCAE v.6 grading DLT according to new grading system? NCT03276572 1 1 Gr 4 TCP 18,000k/uL Gr 4 Gr 3 No NCT04886986 2 1 Grade 2 and 1 Grade 3 TCP delaying cycle 2 for >3 weeks - Gr 2, Gr 3 Unchanged Yes NCT02913196 1 Grade 3 Hypertension - Gr 3 Unchanged Yes NCT04576871 2 1 Gr 4 TCP 11,000 K/uL Gr 4 Gr 3 No 1 Gr 3 Hepatic failure - - Unchanged Yes NCT04506567 11 2 patients with G1 TCP delaying C3> 2 weeks - Gr 1 Unchanged Yes 2 G2 TCP delaying D15/C3> 2 weeks - Gr 2 Unchanged Yes 2 G3 TCP delaying D15/C3> 2 weeks - Gr 3 Unchanged Yes 5 G4 TCP 11,000 K/uL Gr 4 Gr 3 No 21,000 K/uL Gr 4 Gr 3 No 23,000 K/uL Gr 4 Gr 3 No 18,000 K/uL Gr 4 Gr 3 No 12,000 K/uL Gr 4 Gr 3 No

The retaining kdo transferase that synthesizes Escherichia coli K13 capsule is deeply divergent from structurally homologous enzymes

Real-world outcomes of [ ¹⁷⁷ Lu]Lu-PSMA-617 ( ¹⁷⁷ Lu-PSMA-617)in taxane-naïve patients with metastatic castration-resistant prostate cancer (mCRPC): A prostate cancer disease observation (PRECISION) data platform analysis.

81 Background: In the PSMAfore clinical trial, 177 Lu-PSMA-617 achieved a PSA50 (defined as a ≥50% reduction in prostate-specific antigen [PSA] from baseline) response rate in 58%, a median radiographic progression-free survival (PFS) of 12 months, and a median overall survival (OS) of 25 months among taxane-naïve patients with mCRPC who had received one prior androgen receptor pathway inhibitor (ARPI). The aim of the present study was to evaluate the real-world effectiveness of 177 Lu-PSMA-617 in taxane-naïve patients with mCRPC who had received one or more prior ARPIs. Methods: This retrospective, observational study included taxane-naïve adults with mCRPC initiating 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, after ≥1 prior ARPI. All data for the study were extracted from the PRECISION data platform, a harmonized dataset of patients with advanced prostate cancer in the US treated in a variety of clinical settings. The index date was the date of 177 Lu-PSMA-617 initiation. Patient characteristics and PSA response rates were evaluated descriptively. PFS, defined as the time from 177 Lu-PSMA-617 initiation to progression or death, was estimated using Kaplan–Meier methodology. Results: A total of 500 patients were included. The median age was 75 years, 75% of patients were White and 8% Black, and 18% were treated in urology centers while 82% were treated in oncology centers. The most common site of metastasis was bone (77%), followed by lymph node (21%), visceral (12%), and unknown (5%). Overall, 51% had received 1 previous ARPI while 49% had received ≥2. The median baseline PSA was 26.7 ng/mL (interquartile range [IQR] 10−105 ng/mL) and the median time from mCRPC diagnosis to 177 Lu-PSMA-617 initiation was 23.6 months. The median number of 177 Lu-PSMA-617 cycles received was 4 (IQR 2−6). Among 219 patients with available PSA measurements both before and during 177 Lu-PSMA-617 treatment (representing 44% of the cohort), PSA response rates were as follows: PSA50 in 137 (63%), PSA80 in 86 (39%), and PSA90 in 56 (26%) patients. Overall, the median PFS was 13.5 months (95% confidence interval 11.7–14.7 months). Conclusions: The effectiveness of 177 Lu-PSMA-617 as a standard-of-care treatment in real-world, taxane-naïve patients with mCRPC who had received prior treatment with ≥1 ARPI is consistent with results from the PSMAfore trial, confirming the applicability of those findings to the real-world population now eligible for 177 Lu-PSMA-617. Further research on sequencing 177 Lu-PSMA-617 after one or more prior ARPIs in taxane-naïve patients with mCRPC is needed to guide optimal treatment sequencing in clinical practice.

Aggressive variants and clinical patterns of progression in real-world metastatic hormone-sensitive prostate cancer (mHSPC).

118 Background: With the evolving treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC), including androgen deprivation therapy (ADT) in combination with androgen receptor pathway inhibitors (ARPI), docetaxel (D) or triplet therapy, understanding the patterns of progression, particularly the emergence of aggressive variants of prostate cancer (AVPC), is increasingly critical. This study investigates the clinical and molecular features at progression and their impact on outcomes. Methods: This is a multicenter retrospective study in mHSPC patients (pts), treated with ADT, ADT + ARPI (abiraterone, enzalutamide or apalutamide), ADT + D or triplet therapy between 2005 and 2025. Baseline clinicopathologic features, follow-up duration, time to progression, and AVPC, defined as at least one of Aparicio criteria (Aparicio, CCR 2016), were assessed at castration-resistant prostate cancer (CRPC). When available, AVPC molecular alterations in PTEN , TP53 or RB1 (AVPCm) determined by next generation sequencing (NGS) were collected. Outcomes included time to CRPC-free survival (CRPC-FS) and overall survival (OS) assessed by Kaplan Meier and the chi-square test was used to assess the association between categorical variables. Results: 442 pts were included: 112 treated with ADT+D, 90 with ADT, 212 with ADT + ARPI and 28 with triplets. Median age was 69,7 years (range 44,2-92,8). 67,5% presented de novo stage IV, 15,4% visceral metastases, 56,8% high volume disease and 50,8% high risk disease. With a median follow-up of 40,8 months (range 3-223), 222 (49,4%) of pts had died and 266 (59,2%) developed CRPC. Among 173 CRPC pts with sufficient clinical data, AVPC were identified in 80 (48,24%) including neuroendocrine differentiation (by biopsy or serum markers) in 9 (5,3%), with 31 (18,2%) of pts presenting >2 criteria. Short time to CRPC was the most common criteria (25,6%). All pts treated with triplet therapy progressed with AVPC. Among AVPC pts with NGS, AVPC-m was present in 10 out of 36 (27,8%). Among pts with baseline mutations in RB1 , PTEN or TP53 , 23 of 48 (47,9%) progressed with AVPC. Pts with high volume disease, visceral metastases and de novo stage IV progressed more frequently with AVPC (p=0.01, p<0.001 and p=0.03 respectively). Median CRPC-FS and OS for the global cohort were 26,2 and 51,7 months respectively. Patients with AVPC had significantly shorter CRPC-FS (26,8 vs 11 months p<0.001) and OS compared to non-AVPC (60,2 vs. 31,7 months, p<0.001). Treatment at progression included ARPI (20,3%), taxane regimen (19,9%), platinum-based regimens (3,4%), or clinical trial enrollment (6,4%). Conclusions: A clinically meaningful proportion of mHSPC pts progress with AVPC, especially those with high volume disease and visceral metastases associated with remarkably poor prognosis. Early recognition and treatment intensification is critical in these pts.

Revisiting bioluminescence and sucrose utilization in aquatic pathogens Vibrio harveyi and V. campbellii using genome-wide in silico mapping and phenotyping

Clinical outcomes of patients with grade group 1 prostate cancer with extraprostatic extension: Results from up to 25 years of follow-up.

387 Background: Grade Group 1(GG1) prostate cancer is typically an indolent disease; however, there are reports of non-organ confined disease on radical prostatectomy (RP). We sought to examine the long-term oncologic outcomes of patients with GG1 prostate cancer who had extraprostatic extension (EPE), bladder neck invasion (BNI), and/or seminal vesical invasion (SVI) confirmed on RP histopathology. Methods: This was a retrospective cohort study examining all patients at our large quaternary institution. Patients with GG1 and pT3 disease on final radical prostatectomy specimen were identified, and pathology slides were re-reviewed by a dedicated genitourinary pathologist to confirm diagnosis. Those without follow-up were excluded. Outcome variables of interest included post-operative PSA, biochemical recurrence (BCR), metastatic disease, and overall survival. Results: We identified 50 patients at our institution that had confirmed GG1 and EPE on RP final pathology between 2000-2022. Our primary cohort consisted of 40 men as 10 had no follow-up data available. Patient characteristics are summarized in Table 1. Median follow-up was 15 years (interquartile range, 5-18 years). 4 patients (10%) experienced BCR, occurring after an average of 8.6 years (range 3-19 years); of the patients that developed BCR within 10 years (N=3), all had positive surgical margins, while the 1 patient that developed delayed BCR had negative margins. 6 men developed a detectable PSA value after an average of 7.6 years but did not cross the threshold for BCR (i.e. 0.2 ng/mL). No patient developed metastatic disease or death from prostate cancer. There were 8 deaths reported in the cohort from other causes. Conclusions: Our study shows that long-term clinical outcomes for patients with GG1 are favorable despite having pT3 disease. With a median follow-up of 15 years, we did not observe any cases of metastatic disease or prostate cancer specific death. While BCR was reported, it occurred in a delayed pattern. Baseline characteristics. Variable Value (N=40) Age, median (IQR) 58 (52 – 64) Pre-operative PSA, mean (SD) 4.5 (3.3) Final Pathology, number (%)  T3a EPE 33 (83%)  T3a BNI 6 (15%)  T3a EPE and BNI 1 (2%) Nodal pathology, number (%)  NX 31 (78%)  N0 9 (22%) Surgical margin status, number (%)  Negative 21 (53%)  Positive 19 (47%) Surgical approach, number (%)  Open 20 (50%)  Laparoscopic 5 (13%)  Robot-assisted 15 (32%) EPE, number (%)  Focal 23 (58%)  Established 17 (42%)

Impact of Anode to Cathode Crossover in Lithium‐metal Batteries With High‐Nickel Cathodes

ABSTRACT The advancement of high‐energy‐density lithium‐metal batteries (LMBs) is hindered by the chemical instability of both lithium‐metal anode and high‐nickel layered oxide cathodes. While cathode‐to‐anode crossover is well‐documented, the reverse process of anode‐to‐cathode crossover remains underexplored. Here, we systematically investigate such crossovers and the degradation pathway in pouch cells with a localized high‐concentration electrolyte, comparing NMC622, NMC811, and NMC90 cathodes paired with lithium‐metal and graphite anodes. Despite delivering higher initial capacities, LMBs exhibit faster capacity fade under long‐term cycling at 45 °C. To isolate cathode‐side degradation, galvanostatic electrochemical impedance spectroscopy (GEIS) measurements of cycled cathodes paired with delithiated lithium iron phosphate (LFP) counter electrodes reveal significantly higher charge‐transfer resistance in cathodes cycled with lithium‐metal. Surface characterization via X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) reveals greater electrolyte decomposition on cathodes cycled with lithium metal, leading to thicker, more organic‐rich cathode–electrolyte interphases (CEIs), consistent with the elevated charge‐transfer resistance observed in GEIS measurements. Notably, NMC90 shows the most pronounced CEI thickening, linking higher cathode surface reactivity to greater susceptibility to anode‐to‐cathode crossover. This work presents compelling evidence of crosstalk degradation originating from lithium‐metal anodes and underscores the importance of cross‐interface stability for the design of durable LMBs.

Metformin suppresses PPARδ-driven CD47 transcription to enhance macrophage phagocytosis in lung cancer

Triplet therapy with ADT, darolutamide, and biweekly docetaxel for high-risk metastatic castration-sensitive prostate cancer (TRIC): An open-label, single-arm phase II clinical trial.

TPS272 Background: Treatment strategies for metastatic castration-sensitive prostate cancer (mCSPC) have evolved substantially. Historically, androgen deprivation therapy (ADT) or combined androgen blockade (CAB) was standard; however, although ADT is initially effective, most patients develop resistance and progress to castration-resistant prostate cancer (CRPC). The prognosis after progression to metastatic CRPC (mCRPC) remains poor, with median overall survival (OS) reported at 9–35 months. To improve outcomes, intensive upfront treatment for mCSPC has become a focus. The ARASENS trial showed that ADT plus darolutamide (DAR) and triweekly docetaxel (DTX) significantly improved OS compared with ADT plus DTX in high-risk mCSPC. Our institution developed the Canazawa risk classification, defining high-risk disease as meeting at least two of the following: Gleason pattern 5, bone scan index (BSI) ≥1.5, and lactate dehydrogenase (LDH) ≥300 IU/L. Although ARASENS trial used DTX 75 mg/m² every three weeks for up to six cycles, this dose often causes severe toxicities in Japanese patients. In prior CRPC studies, we found that biweekly DTX 35 mg/m² maintained efficacy with fewer adverse events. Based on these results, we hypothesize that triplet therapy with ADT, DAR, and low-dose biweekly DTX may offer a favorable balance of efficacy and safety in Japanese patients with high-risk mCSPC. This phase II study will evaluate the efficacy and safety of this modified regimen. Methods: This single-arm, open-label phase II trial will enroll 30 patients with high-risk mCSPC at Kanazawa University Hospital by December 2029. After consent and histologic confirmation, patients will receive oral darolutamide twice daily for 18 weeks, LHRH analogue every 12 weeks unless surgically castrated, and intravenous DTX 35 mg/m² every two weeks for nine cycles (18 weeks). After chemotherapy, darolutamide and LHRH analogue will be continued. Patients will be assessed at baseline, day 1 of each cycle, at cycle 9 completion, and every three months thereafter. The primary endpoint is PSA response rate, defined as a ≥95% PSA decline from baseline at 3 and 6 months. Secondary endpoints include OS, time to castration resistance, radiographic and clinical progression-free survival, undetectable PSA rate, time to neuroendocrine and double-negative prostate cancer, symptomatic skeletal event (SSE)-free survival, time to first SSE, pain progression, subsequent therapy, cabazitaxel use, performance status decline, opioid use ≥7 days, safety, adverse events, and correlations between serum CCL2/CCL5 levels and treatment response. Clinical trial information: CRB4180005 .

Prognostic and genomic implications of HER2 expression in metastatic prostate cancer.

252 Background: Evidence regarding the prevalence and clinical or biological relevance of Her2 expression in metastatic prostate cancer (mPC) remains limited. Methods: 52 patients (pts) with mPC (48 mCPHS, 4 mCRPC) were retrospectively analyzed. HER2 IHC was performed on FFPE primary and/or metastatic samples using the Dako HercepTest (Agilent platform), scored per gastric/solid-tumor criteria (0, 1+, 2+, 3+). Clinical and laboratory parameters were correlated with HER2 status (0 vs ≥1+). Genomic profiling included TP53, RB1, PTEN, and BRCA1/2. Progression-free survival (PFS) was defined from 1st-line therapy start to progression or death; overall survival (OS) from metastatic diagnosis. Survival was estimated by Kaplan–Meier and compared by log-rank test. Results: HER2 ≥1+ was observed in 59.6% of pts (IHC 1+ = 17%, 2+ = 21%, 3+ = 21%). Baseline characteristics are summarized in Table 1. HER2 0 tumors showed numerically higher rates of adverse clinical features, including ISUP 5 (50% vs 26%), ECOG ≥2 (21% vs 11%), visceral metastases (29% vs 16%), elevated LDH (43% vs 26%), and high-volume disease (57% vs 53%), none reached statistical significance (all p > 0.1). Molecularly, HER2 0 tumors were enriched for BRCA1/2 (24% vs 11%, p = 0.18), TP53 (58% vs 29%, p = 0.11), RB1 (42% vs 14%, p = 0.09), and PTEN (37% vs 7%, p = 0.04) alterations. The only TP53/RB1/PTEN triple-hit occurred in a HER2 0 tumor. No ERBB2 mutations were detected. Median PFS with 1st-line therapy in M1-HSPC pts was numerically shorter for HER2 0 versus HER2 ≥1+ (11.2 vs 16.8 months; HR 1.42, p = 0.18), with consistent trends across chemotherapy and non-chemotherapy regimens. OS was immature (median follow-up 17 months; 26% deaths). None of the pts received HER2-directed ADCs. At the time of submission, genomic results were available for 22 pts; sequencing of 20 additional cases is ongoing, while 10 were not evaluable due to tissue limitations. Conclusions: HER2 expression (IHC ≥1+) was present in approximately 60% of mPC cases. Although not statistically significant, HER2 0 tumors showed enrichment in TP53/RB1/PTEN/BRCA1/2 alterations and a trend toward shorter PFS, consistent across treatment subgroups. These findings suggest that loss of HER2 expression may define a genomically adverse subset of mPC that warrants further validation. Patient characteristics. Age, years – median (range) 69 (51–91) ECOG PS – n(%)  0 20 (38.5)  ≥1 32 (61.5) HER2 expression (IHC) – n(%)  0 21 (40.4)  1+ 9 (17.3)  2+ 11 (21.2)  3+ 11 (21.2) HER2 tested Prostate Lymph node Extranodal metastasis Primary + metastatic site 46 (88.5%)1 (1.9%)2 (3.8%)3 (5.8%) Genomic alterations – n(%)  BRCA2 4/22 (18%)  BRCA1 1/22 (4.5%) Triple hit (PTEN+p53+RB1) 1/22 (4.5%) First metastatic presentation – n(%)  mHSPC recurrent LV 5 (9.6)  mHSPC de novo LV 13 (25.0)  mHSPC recurrent HV 1 (1.9)  mHSPC de novo HV 29 (55.8)  mCRPC 4 (7.7) Sites of disease – n(%)  Bone 41 (78.8)  Lymph nodes 38 (73.1)  Lung 10 (19.2)

Four year mortality and quality of life after ICU treatment for COVID 19 related acute respiratory distress syndrome

Abstract Severe COVID-19 leading to ARDS and ICU admission is associated with high early mortality, yet data on long-term outcomes and societal burden remain limited, particularly in Central and Eastern Europe. To describe 4-year mortality, patient-reported functional status and health-related quality of life (HRQoL) among ICU-treated COVID-19 ARDS patients, and to explore early factors associated with short- and long-term mortality as well as long-term recovery. Single-center retrospective–prospective cohort study with structured 4-year telephone follow-up. 283 adults treated in the Temporary ICU Hospital in Zielona Góra, Poland (December 2020–July 2021). Follow-up interviews were completed in 81 of 157 confirmed 4-year survivors. Associations with 30-day mortality and late mortality (among 30-day survivors) were explored using multivariable logistic regression. Survivors completed a structured interview assessing HRQoL (EQ-5D-5 L/EQ-VAS), dyspnoea severity assessed with the mMRC scale, functional status assessed with PCFS, fatigue, brief cognitive screening items, return to work, rehabilitation use, and financial burden. A cumulative post-ICU impairment score (0–6 domains) was constructed. Cost estimates were exploratory and based on public ICU reimbursement rates and patient-reported rehabilitation burden. Thirty-day mortality was 29.0%, and cumulative 4-year mortality was 45%. In adjusted analyses, older age and higher white blood cell count at ICU admission were associated with mortality endpoints (model discrimination up to AUC 0.86, depending on endpoint). Among 4-year survivors, 27.5% reported clinically relevant fatigue, 46.8% insomnia, and a substantial proportion reported persistent limitations across functional and EQ-5D domains. Rehabilitation was reported by 39% and was associated with lower QALY, likely reflecting greater baseline impairment. Median 4-year QALY was 3.7, varying significantly by fatigue, dyspnoea, return-to-work status, and subjective cognitive complaints. Among ICU-treated COVID-19 ARDS patients, long-term mortality remained high and many survivors reported persistent multidomain impairment years after discharge. These findings support structured post-ICU follow-up pathways and targeted rehabilitation and occupational support for long-COVID survivors.

The Prolaris test on diagnostic biopsy for localized prostate cancer prognosis across risk groups and management: An individual participant data meta-analysis.

394 Background: Tools to risk stratify localized prostate cancer are limited. We sought to conduct a robust, individual participant data (IPD) meta-analysis of the performance of Prolaris from diagnostic biopsy in localized prostate cancer. Prolaris is based on a combined clinical risk (CCR) score that categorizes individual patient risk into low, intermediate, or high risk based on locked and validated active surveillance (AS) and multi-modal therapy thresholds. Methods: A systematic literature search was performed, and IPD were collected where possible to perform a two-step IPD analysis. The primary endpoint was a composite of distant metastasis (DM) and prostate cancer specific mortality (PCSM), also analyzed individually. Within each cohort Cox proportional hazards models were fit adjusting for treatment received. Random-effects meta-analyses with Knapp-Hartung adjustment were used to create combined hazard ratio (HR) estimates across studies. Results: Fourteen eligible studies included 8,480 total patients, of which 7,926 had IPD. The cohort consisted of 20.0%, 33.9%, 32.5%, and 13.6% NCCN Low-, Favorable Intermediate-, Unfavorable Intermediate-, and High-Risk disease, respectively. Initial management was 42.9% non-interventional (e.g. AS), 23.6% surgery, 16.4% radiation therapy (RT), and 13.0% RT plus androgen deprivation therapy. CCR was prognostic for composite DM-PCSM after accounting for treatment received (HR 2.28 (95% CI 1.92, 2.62), p=9.14x10-9) with insignificant heterogeneity (I2 =14%, p=0.3) and was also individually prognostic for DM (p=1.87x10⁻⁶) and PCSM (p=3.14x10⁻⁴). Influence analyses demonstrated that results were not materially influenced by any one study. Additional meta-analyses demonstrated that CCR adds independent prognostic information to Gleason, CAPRA, or NCCN (all p<10) and that Prolaris Risk Groups are prognostic for composite DM-PCSM, as well as for individual endpoints (all p<0.05). Conclusions: Prolaris improves prognostication across NCCN Risk Groups and treatment strategies in localized prostate cancer. Prognostic value persists after adjusting for initial treatments and established clinical factors, highlighting utility in supplementing conventional risk models.

The Rise of Aqueous Selenium‐Based Batteries: Challenges, Strategies, and the Path Forward

ABSTRACT Aqueous metal‐selenium batteries (AMSeBs) have emerged as promising candidates for safe, cost‐effective, and high‐energy‐density energy storage, yet their development is hindered by challenges spanning electrode stability, reaction reversibility, and electrolyte compatibility. This review systematically explores the thermodynamic and electrochemical landscape of AMSeBs, integrating theoretical analysis with experimental advances to establish a rational design framework. First, by evaluating key parameters, including electrode potentials, volume change rates, solubility of metal selenides, and energy metrics, we identify promising systems such as Zn‐Se and Cu‐Se, along with unexplored candidates like Fe‐Se and Ga‐Se. Second, selenium‐based cathodes are categorized into three types, elemental Se & Se x S y composites, organic selenides, and transition metal selenides, with emphasis on multi‐electron transfer mechanisms, particularly the six‐electron Se 4+ /Se 2− redox pathway, which offers a route to overcome capacity limitations. Third, strategies for stabilizing metal anodes, expanding the electrochemical stability window of aqueous electrolytes, and mitigating shuttle effects are critically discussed. Finally, we outline future directions, including interface engineering, artificial intelligence‐assisted material screening, and flexible device integration, providing a roadmap toward high‐performance AMSeBs for next‐generation energy storage applications.

Prussian Blue Analog as a Functional Additive for Restoring Sulfide Solid Electrolytes: Enhancing Moisture Stability in All‐Solid‐State Batteries

Abstract Sulfide‐based solid‐state electrolytes (SSEs) hold significant potential for all‐solid‐state batteries (ASSBs), but their severe degradation upon exposure to moisture remains a major barrier to their practical application. In this work, Prussian blue analogs (PBAs) are introduced as functional additives into the SSEs to enhance moisture stability. It is demonstrated that PBAs can not only suppress moisture‐induced degradation of SSEs but also actively reverse it, offering a reviving function that restores the electrochemical performance of previously degraded SSEs. When PBAs are simply postmixed with previously degraded SSEs under 5% relative humidity for 6 h, the resulting cells exhibited an average Coulombic efficiency of 99.9% over 500 cycles with 95.2% capacity retention. This restoring behavior is attributed to the open‐framework structure of PBAs, which provides abundant interstitial and coordination sites that facilitate the efficient absorption of hydrated water molecules and evolved gases such as H 2 S. In addition, PBAs exhibit a ductile nature that mitigates the increase in interfacial resistance typically induced by conventional additives, thereby preserving high ionic conductivity of SSEs. These results highlight PBAs as next‐generation multifunctional additives―capable of both protecting and recovering sulfide SSEs, offering a viable route toward stable and durable sulfide‐based ASSBs assembled under ambient conditions.

Dissecting a two-domain alginate lyase of family PL6 reveals a mechanistic basis for substrate specificity and enzyme activity

PAM50 intrinsic subtyping and Decipher genomic classifier in biochemically recurrent prostate cancer after prostatectomy: Implications for ADT selection.

390 Background: PAM50 captures prostate cancer lineage (Luminal B vs Non-Luminal B [Luminal A + Basal]) and may inform response to androgen-pathway therapy, while Decipher (GC) guides selection of ADT with salvage radiotherapy (sRT). We examined how PAM50 tracks with GC and whether ADT’s association with metastasis varies by subtype. Methods: Single-institution, prospectively collected post-RP cohort with biochemical recurrence. RP tissue underwent PAM50 and Decipher testing. Primary endpoint was metastasis; death before metastasis was a competing risk. We fit a Fine–Gray model with subtype (Lum B vs Non-Lum B), ADT with first-course sRT (yes/no), and the subtype×ADT interaction. Time origin was radical prostatectomy. Among 122 analyzable men, ADT distribution at time 0 was: Lum B/no ADT = 12, Lum B/ADT = 40, Non-Lum B/no ADT = 13, Non-Lum B/ADT = 57. Results: N=123 overall (LumA 30, LumB 53, Basal 40). Decipher differed by subtype: median GC LumA 0.60 (IQR 0.30–0.80), LumB 0.80 (0.60–0.90), Basal 0.70 (0.40–0.80); p=0.004. Decipher Risk groups (<0.45, .45-.59, .6-.84, >.84) also differed (p=0.006); GC 0.85–1.00 occurred in 41.5% of LumB vs 22.5% Basal and 13.3% LumA. Many Non-Lum B crossed thresholds commonly used to support ADT with sRT: GC > 0.45 ~63%, GC ≥ 0.60 ~53%, GC ≥ 0.85 ~19% (weighted from LumA+Basal). Basal had more positive margins (65.0% vs 43.4% LumB vs 23.3% LumA; p=0.026). In the competing-risks model (19 metastasis, 3 competing deaths), ADT was associated with lower metastasis hazard in Lum B (sHR 0.10, 95% CI 0.038–0.266; p<0.001; reference = Lum B/no ADT). Non-Lum B vs Lum B (no ADT) trended toward lower hazard (sHR 0.23, 95% CI 0.044–1.206; p=0.082). The interaction (Non-Lum B×ADT) was not significant (sHR 2.49; p=0.364), providing no evidence that the ADT association differed by subtype. Descriptively, the highest metastasis incidence occurred in Lum B/no ADT. Conclusions: PAM50 correlates with genomic risk (Lum B highest GC), yet many Non-Lum B tumors also meet GC cutpoints often used to support ADT with sRT. In this cohort ADT was strongly associated with lower metastasis, and we did not detect a subtype-specific interaction (limited by 19 events and observational treatment assignment). Clinical implication: Do not withhold ADT solely because a tumor is Non-Lum B—particularly when Decipher is high—while Lum B appears to derive the greatest benefit. Basal’s higher margin positivity and longer RP→sRT interval suggest a locoregional-failure phenotype, supporting evaluation of earlier and/or locally intensified salvage.

Shifting 177Lu-PSMA-617 upstream in mCRPC: A meta-analysis of randomized trials stratified by taxane exposure.

199 Background: 177Lu-PSMA-617 is approved for post taxane, post ARPI mCRPC based on the VISION trial. With the emergence of PSMAfore and earlier line data, there is growing interest in if radioligand therapy should be moved upstream, particularly in taxane naive, ARPI resistant disease. To inform sequencing decisions, we compared treatment effect estimates in post taxane versus taxane naive settings using pooled randomized evidence. Methods: Randomized controlled trials evaluating 177Lu-PSMA-617 in mCRPC with available hazard ratios for radiographic progression free survival (rPFS) or overall survival (OS) were included. Trials were grouped by taxane exposure status (post taxane vs taxane naive). Fixed effect models were used for figure presentation, and Hartung–Knapp random effects models were reported in text to account for small study numbers. PSMAfore was included using IPCW adjusted OS estimates to address crossover. Results: Four trials (VISION, PSMAfore, TheraP, Satapathy; n=1,559) contributed to rPFS pooling. The fixed effect pooled HR for rPFS was 0.52. In taxane naive trials (PSMAfore and Satapathy), HR was 0.54 (95% CI, 0.43 - 0.64), while post-taxane trials (VISION and TheraP) showed HR 0.50 (95% CI, 0.40 - 0.64). Using HK adjustment, the pooled HR for rPFS was 0.54 (95% CI 0.10–2.93) in taxane naive disease and 0.50 (95% CI 0.03–9.03) post taxane. OS synthesis using IPCW adjusted PSMAfore and VISION showed a pooled HR of 0.62 (95% CI 0.52–0.73). All estimates favored radioligand therapy with consistent direction of effect across subgroups. Conclusions: The relative benefit of 177Lu-PSMA-617 appears comparable in taxane naive and post taxane mCRPC, suggesting that treatment activity is preserved when used earlier in the disease course. These findings support a biology driven sequencing model in which PSMA PET based selection, rather than taxane exposure history alone, may guide placement of radioligand therapy. Prospective sequencing focused trials will be essential to validate optimal timing and ensure equitable implementation.

Associations between political orientation and allyship: Evidence from potential allies and their LGBTQ+ close others

Abstract To support the LGBTQ+ community , many straight , cisgender individuals position themselves as allies to their cause. It is possible that those identifying as liberal may champion LGBTQ+ causes more passionately than those identifying as conservative , though it is also possible that liberals’ self-perceptions do not align with how LGBTQ+ individuals perceive them. In this study , we systematically investigated the relationship between political orientation and allyship to the LGBTQ+ community. We recruited 378 dyads composed of a cisgender , straight individual and an LGBTQ+ close other. Findings suggested that self-perceptions of allyship (from cisgender , straight individuals) were largely consistent with evaluations from LGBTQ+ close others. In line with our expectations , on average , liberals (compared to conservatives) both viewed themselves and were perceived as better allies. However , there was a small but significant tendency for liberals to overestimate their allyship relative to conservatives. In addition , exploratory analyses revealed other-perceived allyship was positively associated with higher interpersonal trust , underscoring allyship’s importance in close relationships. These findings contribute to a growing understanding of the ideological and interpersonal antecedents of allyship and inform strategies for fostering stronger , more authentic relationships with the LGBTQ+ community. The stage 1 protocol for this Registered Report was accepted in principle on 11/15/2024. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/2Q7W6 .

Mortality risk with androgen receptor pathway inhibitors: Real-world evidence.

64 Background: Androgen deprivation therapy (ADT) is the standard of care in advanced prostate cancer (PCa). In recent years, androgen receptor pathway inhibitors (ARPIs) have been introduced as important additions to ADT to further suppress androgen signaling and improve oncologic outcomes, and ADT+ARPI treatment is now guideline-recommended standard of care. While ARPIs prolong cancer survival, accumulating evidence reinforces longstanding concerns that they may exacerbate cardiovascular (CV) risk; a recent systematic review (n=22,000) demonstrated that addition of ARPIs to ADT was associated with approximately a 2x increase in the risk of all-grade CV events (RR 1.75) and grade ≥3 CV events (RR 2.10). Since CV events contribute significantly to mortality in this population, survival outcomes are of particular concern. Using real-world data, the objective of this study was to evaluate the risk of all-cause mortality (ACM) after ADT initiation for patients treated with ADT+ARPI vs. ADT without an ARPI. Methods: Data were collected from the Decision Resources Group (DRG, now Clarivate) Real World Evidence repository, including >300 million patients' medical and pharmacy claims and EHR data. The analysis set included PCa patients who received ≥ 1 ADT injection (99% of patients started ADT within 2010-2020). Kaplan-Meier survival curves were constructed, and Cox regression was used to compare ACM rates between patients on ADT+ARPI vs. ADT without ARPI. Results: 44,439 men with PCa were included in the analysis. At 4 years after ADT initiation, ACM risk was higher for patients with ARPI vs. without (25.1% vs 14.4% for the ARPI vs without ARPI groups, respectively). The unadjusted HR was 1.82 (95% CI 1.73-1.91, p<0.001), indicating a statistically significant difference consistent with the KM curve. After adjustment, the adjusted HR for ACM risk in ARPI vs. without ARPI patients remained significant at 1.60 (95% CI 1.37-1.86, p<0.001). Conclusions: While doublet therapy is guideline-recommended standard of care for PCa, addition of ARPI therapy to foundational ADT is associated with a significantly increased mortality risk in PCa patients compared to ADT without ARPI. Extending findings of a prior systematic review of clinical trial data that showed increased CV risk with ARPIs, our real-world analysis of ~45,000 patients also demonstrates an associated increase in ACM risk. This is notable as ARPIs are intended to prolong survival, underscoring the need to proactively assess and manage mortality risk in patients on ADT, particularly when combining ADT with an ARPI. Clinicians should assess baseline CV risk and comorbidities that exacerbate CV disease when initiating ARPI-based doublet therapy and, based on prior real-world analyses (Crawford et al., J Urol, 2024), consider preferential use of LHRH agonists over GnRH antagonists in appropriate patients.