Browse Articles

Optimizing Peptide Ionizable Lipids Enables Efficient and Low‐Toxicity mRNA Delivery for In Vivo Prime Editing and Protein Replacement Therapy

ABSTRACT Highly efficient mRNA lipid nanoparticle (LNP) often presents potential safety risks. Here, we establish a structure–activity relationship framework for peptide ionizable lipids (PILs) to facilitate the rational design of safe and effective mRNA‐LNPs. The PIL structure comprises three modular components: building block, side‐chain length, and hydrophobic tail. Through systematic optimization, a lead compound (Dab4) with four building blocks and a moderate side chain length was identified, demonstrating minimized hepatotoxicity while maintaining superior delivery performance. Leveraging this framework, a series of Dab4‐derived PILs with three tail types, including alkyl (a‐tail), ester (aat‐tail), and hydroxyl (e‐tail), were synthesized. This tail chemistry determined organ tropism, with B12‐a13Dab4 (a‐tail) showing optimal performance in the liver. The B12‐a13Dab4 LNP exhibited significantly higher hepatic delivery efficiency and markedly improved biosafety compared with the FDA‐approved SM‐102 formulation. Moreover, B12‐a13Dab4 LNP efficiently triggers in vivo prime editing by co‐delivering PE7 mRNA and epegRNA, and achieves significant therapeutic effects in a Hereditary Tyrosinemia Type 1 (HT‐1) model through repeated delivery fumarylacetoacetate hydrolase (FAH) mRNA. This study establishes rational design principles for PILs that strike a balance between efficacy and safety, offering a versatile mRNA‐LNP platform for the advancement of gene editing and protein replacement therapies.

Engineered Perfusable Hepatic Fibrosis Model via Embedded Sacrificial Bioprinting Recapitulates Stiffness‐Driven Fibrogenesis

ABSTRACT Hepatic fibrosis, as the common pathological endpoint of chronic liver diseases, is characterized by a self‐perpetuating vicious cycle comprising extracellular matrix (ECM) driven liver tissue stiffening and sustained hepatic stellate cell (HSC) activation. Although existing studies have simulated fibrotic microenvironments using 2D models with tunable matrix stiffness or static 3D cultures, these models lack engineered hepatic sinusoidal vasculature and dynamic mechanical stimulation within 3D ECM contexts. This study employed embedded sacrificial bioprinting to construct functional liver sinusoid‐mimetic vascular networks within hydrogel matrix of precisely tunable elastic modulus, establishing a dynamically perfused in vitro liver fibrosis model. Experimental validation demonstrated that matrix stiffness directly drives HSC activation, inducing marked myofibroblastic transdifferentiation. Furthermore, compared to static models, 3D dynamic perfusion significantly enhanced hepatocyte sensitivity to high‐stiffness matrix, more accurately replicating the functional decline of hepatocytes in fibrotic microenvironments observed in vivo. More critically, the biomimetic in vitro platform established in this study presents a potential avenue for evaluating pharmacotherapeutic interventions against liver fibrosis. Through targeted inhibition of key signaling hubs, we achieved partial reversal of HSC activation on stiff matrix and partial recovery of liver tissue function. Overall, by simultaneously integrating matrix stiffness modulation, 3D multicellular interactions, and hemodynamic stimulation, this work effectively addresses the insufficient responsiveness of hepatocytes to mechanical cues in conventional models due to inadequate mechanical stimulation. This approach provides a robust framework for faithfully recapitulating the pathophysiological progression of liver fibrosis in vitro through precise tuning of ECM mechanical properties, thereby offering a promising platform for future drug screening and therapeutic assessment.

The amyloidogenic C-terminal region of TMEM106B modulates lipid membrane biophysical properties: Functional and pathological insights

Impact of treatment approaches on survival in bulky node-positive penile squamous cell carcinoma: A National Cancer Database analysis.

3 Background: For patients with cN2–N3 penile squamous cell carcinoma (SCC), multimodal therapy with chemotherapy and surgery is the standard of care. Although NCCN designates neoadjuvant cisplatin-based chemotherapy as preferred for bulky or fixed nodal disease, its real-world adoption and impact on survival are not well defined. To address this gap, we evaluated national outcomes to characterize the clinical benefit and utilization of perioperative chemotherapy in node-positive penile SCC. Methods: Using the National Cancer Database (2004–2022), we identified patients with any T, cN2–N3, and M0 penile SCC who received at least one definitive treatment modality. Patients were grouped as: lymph node dissection (LND) alone, adjuvant chemotherapy after LND, neoadjuvant chemotherapy followed by LND, LND with adjuvant radiation, or chemoradiation (CRT) without surgery. Overall survival (OS) was compared using multivariable Cox regression adjusting for age, comorbidity, race, insurance, income, and facility type. Results: Among 907 eligible patients, median age was 64 years, and 55% were treated at academic centers. Treatment distribution was: LND only (36.2%), adjuvant chemo (35.3%), neoadjuvant chemo (9.4%), LND + RT (3.8%), and CRT (15.4%). Median OS was 20.5 months for LND only, 31.6 for adjuvant chemo, 39.0 for neoadjuvant chemo, 25.6 for LND + RT, and 17.0 for CRT. On multivariable analysis, both adjuvant and neoadjuvant chemotherapy were independently associated with improved survival compared with surgery alone. Radiotherapy with or without surgery did not significantly improve outcomes. Treatment at academic centers was associated with longer survival. Conclusions: In node-positive penile SCC, integration of chemotherapy with lymph node dissection improves overall survival compared with surgery alone. Neoadjuvant chemotherapy provided the greatest survival benefit but remained markedly underused, administered in only 10 percent of patients with cN2–N3 disease. Radiotherapy without surgery offered no clear advantage. These population-level data validate NCCN-endorsed multimodal management, highlight gaps in the adoption of perioperative chemotherapy, and establish a real-world benchmark for implementing guideline-based multidisciplinary care in advanced penile cancer. Multivariable cox model for overall survival in node-positive penile SCC. Variable Comparator HR (95% CI) p-value Age ≥65 years vs <65 1.32 (1.08–1.61) 0.007 Facility: Academic vs Community 0.78 (0.64–0.96) 0.020 Adjuvant chemo + LND vs LND only 0.79 (0.65–0.98) 0.031 Neoadjuvant chemo + LND vs LND only 0.41 (0.27–0.62) <0.001 LND + RT vs LND only 0.75 (0.49–1.16) 0.193 CRT (no surgery) vs LND only 1.13 (0.89–1.44) 0.325 Charlson-Deyo ≥2 vs 0 1.17 (0.83–1.65) 0.365 Black race vs White 0.86 (0.66–1.14) 0.296

Comparison of outcomes of contemporary immune-check point inhibitors combinations in Black patients versus White patients with metastatic renal cell carcinoma (mRCC).

433 Background: Immune checkpoint inhibitor (ICI)-based combinations, including dual ICI and ICI plus tyrosine kinase inhibitors (TKI), represent the current standard of care for mRCC. However, limited data exists regarding racial differences in treatment outcomes using these combinations. We aimed to compare the effectiveness of ICI combinations in self-identified non-Hispanic Black (Black) versus non-Hispanic White (White) patients with mRCC. Methods: We conducted a retrospective analysis of 600 mRCC patients treated at our institution between 2013 and 2025. Eligible patients had metastatic disease and received ICI combination at any line. Demographics, clinical characteristics, and outcomes were collected via chart review. Overall survival (OS) and time to treatment failure (TTF) were measured from ICI initiation using the Kaplan-Meier method. Univariate and multivariate analyses assessed the association between race and outcomes, adjusting for histology, IMDC risk, and performance status. Results: Among 167 eligible patients, 134 (80%) were White and 33 (20%) were Black, with a median age of 61 years (range 24–84) at the start of ICI. Most patients were male (74%) and had clear-cell histology (81%). ICI combinations were given as first-line therapy in 150 patients (90%), including dual ICI in 67 (41%) and ICI plus TKI in 98 (59%). IMDC risk distribution (good/intermediate/poor) was 22%/52%/26% for White and 10%/52%/39% for Black patients (p = 0.171). The objective response rate (ORR) was higher among White patients (46%) than Black patients (27%) (p = 0.048). Median OS was shorter in Black versus White patients on univariate analysis (HR 1.78 [95% CI 1.09–2.9], p = 0.021), while TTF was similar (HR 0.9 [0.6–1.36], p = 0.63). In multivariate analysis, race was not an independent predictor of OS. Conclusions: In this single-institution study of ICI combinations in mRCC, Black patients exhibited lower response rates and shorter OS compared to White patients. Although the OS difference was not statistically significant after adjusting for multiple strong prognostic factors, these findings suggest potential disparities may still be inherent in ICI combination outcomes between Black and White patients that merit further study in larger, diverse cohorts.

Treatment utilization among patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) in real-world US settings: A prostate cancer disease observation (PRECISION) data platform analysis.

75 Background: Although the number of life-prolonging treatment options for pts with mHSPC has increased, initial real-world evidence has demonstrated slow uptake. This study utilized a large, contemporary, real-world dataset to evaluate the characteristics and treatment utilization among US pts with mHSPC in recent years. Methods: This retrospective, observational study used data from PRECISION, a harmonized dataset on pts with advanced prostate cancer. Adult men who were diagnosed with mHSPC during 01/01/2020–01/01/2024 (index date) and who initiated ≥1 therapy were included; the study period was 01/01/2010–06/30/2025. Pt characteristics were described at index. Treatment utilization was evaluated from index until progression to metastatic castration-resistant prostate cancer, death, or last follow-up. If an androgen receptor pathway inhibitor (ARPI), docetaxel, or radiotherapy was started within 4 months of index/androgen-deprivation therapy (ADT) start, it was considered a first-line (1L) combination; if it was started after >4 months, it was considered treatment intensification. All analyses were descriptive. Results: Among the 27,708 pts who met the inclusion criteria in PRECISION, 72%, 18%, and 10% were treated in community urology, community oncology, and academic oncology centers at index, respectively. Median age was 72 years; 62% were White; 43% were from the US South; 53% had synchronous and 54% had metachronous metastases (2% unknown). Median prostate-specific antigen level was 9 ng/mL (mean, 130 ng/mL). Prior to mHSPC diagnosis, 19% of pts had a prostatectomy and 17% had radiotherapy. Almost half of pts (47%) initiated 1L treatment with ADT monotherapy; 36% initiated 1L ADT + ARPI, 5% 1L ADT + radiotherapy, 2% 1L ADT + docetaxel, 5% 1L ADT + radiotherapy + ARPI or docetaxel, and 5% other regimens. From 2020 to 2023, 1L ADT monotherapy use decreased, while 1L combination use increased (Table). In addition, 19% of pts with 1L ADT monotherapy had evidence of subsequent treatment intensification, mainly the addition of an ARPI. Conclusions: In this study, use of 1L ADT monotherapy declined over time, accompanied by an increase in 1L combinations and treatment intensification. Nonetheless, approximately 1/3 of pts still did not receive a combination or intensification. Further research is needed to understand treatment trends in pts with mHSPC. Treatment patterns by index year. Pts, % 2020(n=5278) 2021(n=6203) 2022(n=7701) 2023(n=8526) 1L ADT monotherapy* 54 52 45 40 Subsequent treatment intensification* 18 19 20 18 1L ADT + ARPI* 29 33 38 42 1L ADT + radiotherapy 5 5 5 6 1L ADT + docetaxel* 3 2 2 1 1L ADT + radiotherapy + ARPI or docetaxel* 3 3 5 7 *p<0.001 for trend across years.

Engineering Bilayer Tandem Catalysts on Si‐Based Photocathodes for High‐performance CO ₂ Reduction to Produce Methane

ABSTRACT Solar‐powered CO 2 reduction through photoelectrochemical (PEC) approaches to produce hydrocarbon fuels, such as methane (CH 4 ), is one of the most promising paths for supplying sustainable fuels. However, the limited light absorption capability and sluggish kinetics restrict the photocatalytic rate and selectivity for hydrocarbon production. Here, we introduce tandem catalysts on photocathodes designed to enhance controlled sequential reactions involving intermediates and thus the selectivity of CO 2 reduction. Specifically, when mounted on Cu/Ag‐Cu bilayer catalysts, the p‐type Si photocathode with a pyramid‐structured surface dramatically improves CO 2 ‐to‐CH 4 conversion, achieving a selectivity of 60.2 ± 3.4% and a working current density of −32.9 ± 1.9 mA cm −2 at −1.1 V vs. RHE. As identified by operando Raman and synchrotron‐radiation Fourier transform infrared spectroscopy and Density Functional Theory, the bottom layer of the Cu/Ag‐Cu catalysts comprises Ag and Cu nanoparticles, which catalyse the initial reduction of CO 2 to form *CO and the creation of *H species dissociated from H 2 O, respectively. The top Cu layer subsequently enables the protonation of *CO to *CHO, ultimately yielding CH 4 . This design of tandem catalysts, coupled with a thorough investigation of the reaction mechanisms, offers a powerful approach toward high‐performance and selective pathways for solar‐powered CO 2 reduction to targeted products.

Spectro‐Temporal Ratiometric Strategy for Thermally Invariant Optical Manometry

ABSTRACT Optical manometry provides noncontact pressure sensing but remains vulnerable to temperature‐induced drift, where thermal expansion and nonradiative relaxation distort luminescence spectra and kinetics. We develop a spectro‐temporal ratiometric approach that combines spectral and time‐gated luminescence channels to decouple pressure and temperature responses and realize thermally invariant optical manometry. Using Y 3 In 2 Ga 3 O 12 :Cr 3+ as a rigid‐lattice host (D q/B ≈ 2.2), lattice stiffness minimizes thermal sensitivity S R,T , while ratiometric detection stabilizes pressure sensitivity S R,p . The resulting thermal‐invariance manometric factor ( TIMF) = S R,p / S R,T reaches ≈7700 K·GPa −1 in the spectral domain and ≈2500 K·GPa −1 in the time‐gated domain, with S R,p up to 51%·GPa −1 . These values exceed ruby benchmarks by two orders of magnitude and surpass conventional lifetime analysis by ∼40 times, enabling accurate, self‐referenced optical pressure mapping under extreme thermo‐mechanical conditions. This work provides luminescent manometry from empirical calibration to a quantitative framework for thermally reliable sensing in coupled fields.

Topologically associating domains define the 3D genome architecture of mouse totipotent-like stem cells

Real-world effectiveness and treatment patterns in patients with locally advanced or metastatic urothelial carcinoma receiving avelumab first-line maintenance in Japan: Long term follow-up from the JAVEMACS chart review study.

674 Background: Avelumab first-line maintenance (1LM) was approved in Japan in February 2021 based on the results of the phase III JAVELIN Bladder 100 trial, which showed an overall survival (OS) benefit in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) after 1L platinum-based chemotherapy (PBC). We report long-term real-world effectiveness and treatment patterns from JAVEMACS, a multicenter retrospective chart review. Methods: Patients with la/mUC who received 1L PBC and initiated avelumab 1LM between February 2021 and December 2023 were identified across multiple centers. Data were extracted from medical charts and integrated into a centralized electronic data capture system. Patient characteristics, effectiveness (OS, progression free survival [PFS], PFS from 1LM start to second-line [2L] progression or death [PFS2]), and treatment patterns were analyzed. Multivariable Cox models were used to identify prognostic factors for OS. Results: The study included 349 patients. At data cutoff (31 May 2025), median observation period was 34.0 months (95% CI, 30.5–36.7). At 1LM start, median age was 73 years (range, 43–93); 74.2% were male; ECOG PS was 0 in 81.4% and ≥1 in 17.5% patients. Primary tumor site was bladder in 50.7% and renal pelvis/ureter in 47.9% patients, and 39.8% had a history of radical surgery. 1L PBC regimen was gemcitabine/cisplatin in 56.2% and gemcitabine/carboplatin in 33.0% patients. Median 1L PBC cycles was 4 (IQR, 4–4). Median duration from 1L PBC start to 1LM start was 19.2 weeks (IQR, 15.4–24.2). At the last follow-up, median 1LM duration was 4.9 months (IQR, 2.1–12.6; < 3 months: 38.1%, ≥3 to ≤12 months: 36.4%, > 12 months: 25.5%); 49 (14.0%) patients were still on 1LM. Of 300 patients who discontinued 1LM, 221 (73.7%) received 2L therapy, with enfortumab vedotin 148 (67.0%) being the most used. Forty-seven (13.5%) patients received curative-intent local therapy (radiation or surgery) to the primary or metastatic sites after 1LM start. Survival results were summarized in the Table. After multivariable adjustment, ECOG PS, liver metastasis at 1L PBC start, serum C-reactive protein, and best overall response to 1L PBC were independent prognostic factors for OS after starting 1LM (all p < 0.05). Conclusions: In this Japanese real-world cohort of la/mUC patients who did not progress after 1L PBC, avelumab 1LM demonstrated favorable long-term outcomes. These findings support routine use and the value of prognostic assessment at 1LM initiation. Median (95% CI), months OS from 1LM PFS from 1LM PFS2* from 1LM Overall (N=349) 30.6 (24.6–40.1) 7.3 (6.0–8.7) 20.2 (16.0–24.6) *From 1LM start until 2L progression or death, whichever occurs first. 1LM, first-line maintenance; 2L, second-line; OS, overall survival; PFS, progression free survival.

SASAN-SPARING: A phase 2 trial of sasanlimab maintenance as bladder-sparing option after neoadjuvant chemotherapy in patients with muscle invasive bladder cancer.

TPS900 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with a high risk of progression, representing a major therapeutic challenge. Adaptive bladder-sparing strategies, which rely on restaging to guide treatment decisions, are being adopted for MIBC management, demonstrating effective disease control while avoiding radical cystectomy (RC)-associated morbidities. This study aims to evaluate a bladder-sparing approach using sasanlimab, a PD-1 inhibitor, as maintenance treatment in patients who achieve a clinical response following neoadjuvant cisplatin-based chemotherapy. Methods: The SASAN-SPARING (HM-8788561) trial is a single-arm, multicentre, phase 2 clinical study that evaluates the efficacy and safety of sasanlimab as maintenance treatment following neoadjuvant cisplatin-based chemotherapy in patients (aged ≥18 years) with treatment-naïve, localized MIBC who are candidates to receive neoadjuvant chemotherapy followed by RC. The study follows an adaptive treatment strategy, where patients receive four cycles of neoadjuvant chemotherapy consisting of cisplatin (70 mg/m2, day 1), and gemcitabine (1000 mg/m2, days 1 and 8) every three weeks. Following chemotherapy, patients are restaged, those achieving a clinical response (defined as cT0/Ta/T1/Tis, normal cytology, and negative imaging) are eligible for bladder preservation and receive sasanlimab (300 mg) subcutaneously every 4 weeks for up to 12 cycles, whereas non-responders (≥cT2) undergo RC. During maintenance, patients are restaged every 12 weeks, in case of progression or loss of response, RC may be considered at the physician’s discretion. The primary endpoint is the bladder-intact overall survival (biOS), at 12 months after the first dose of sasanlimab. Secondary endpoints include clinical response rate, disease-free survival, overall survival, safety, and patient-reported outcomes. The study integrates a comprehensive biomarker program, including whole-genome sequencing of tumour tissue and plasma, the use of circulating tumor DNA (ctDNA) in plasma and urine for tumour assessment and molecular dynamics, and gut microbiome profiling. Correlative analyses aim to refine patient selection and generate hypotheses for future adaptive treatment strategies. A total of 70 patients are planned for enrollment, assuming a 12-month biOS of 81% (H0) and an increase with sasanlimab up to 93% (H1) (one-arm survival test; α = 0.05, β= 0.8). Recruitment started in December 2024, and at the data cutoff, October 2025, 40 patients had been enrolled, of whom 13 initiated sasanlimab maintenance therapy. Clinical trial information: NCT06623162 .

Artificial intelligence versus traditional approaches in multicomponent spectral analysis

Abstract This study explores the use of AI-assisted data handlingin spectrophotometric method development, providing a flexible and globally accessible alternative to traditional manual software algorithms.Quadriderm cream combines four active ingredients: Clioquinol (CLIO), Betamethasone (BETA), Tolnaftate (TOL), and Gentamicin (GEN) with the preservative Chlorocresol (CC). Building on our previous research on complex pharmaceutical mixtures with challenging ratios, this study applied established protocols for CLIO and GEN while focusing on the more analytically demanding ternary subsystem (TOL, BETA, and CC).The integration of AI-enhanced spectral handling and interpretation reduces operator-dependent variability and streamlines the analytical workflow. This includes generating calibration graphs and regression equations, as well as effectively handling scanned spectral data via consecutive prompts. Validation data such as accuracy and precision are assessed to ensure reliability. Furthermore, the system enables intelligent, simultaneous analysis of laboratory mixtures and pharmaceutical formulations, enhancing both efficiency and accuracy. The AI strategy, trained on spectral data supplied and monitored by the expertiseanalyst, can automatically predict optimal wavelengths with minimal interference, while manual handling strategy rely on analyst-driven selection. Two novel approaches were developed: the factorized derivative ratio extraction using double divisor (MAN-[DD- DDE])via Spectra Manager ® software and the automated double divisor derivative ratio (AUTO-[DD-DD]) via AI tools and for resolving ternary mixtures with severely overlapping UV spectra and comparing the results with those of(MAN-[DD- DD])at coincidence points. Linear working ranges were 0.5–5.0 µg/mL (TOL), 3.0–30.0 µg/mL (BETA), and 2.0–20.0 µg/mL (CC); LODs were 0.09, 0.09, and 0.26 µg/mL, respectively. AI-driven data processing strategy matched the accuracy and reproducibility of traditional strategy manipulation while reducing subjective steps and effort. Finally, the UV-spectrophotometric method for pharmaceutical cream analysis was evaluated using the MA Tool (2025) to assess sustainability across green, white, and AI-driven criteria. AI-assisted scoring via Microsoft Copilot enabled rapid, reproducible assessment, yielding a Whiteness Score of 60.9% and providing actionable recommendations for greener and more efficient workflows.

Association of early achievement of ultra-low PSA levels with radiologic progression-free survival (rPFS) in metastatic hormone-sensitive prostate cancer (mHSPC).

73 Background: Ultrasensitive assays allow the measurement of PSA levels below 0.2 ng/mL, which were previously considered undetectable. This may provide a more sensitive assessment of PSA response and treatment efficacy in mHSPC. In the current study, we evaluated the association between early achievement of ultra-low PSA levels and rPFS in patients with mHSPC. Methods: Patients received first-line therapy with androgen receptor pathway inhibitors (ARPIs) plus ADT, ADT with docetaxel, or ADT alone. Serum PSA levels were measured at baseline, 1, 3 months, and thereafter. Patients were stratified into three groups based on the lowest PSA level reached within the first three months: <0.02 ng/mL, 0.02–0.2 ng/mL, and >0.2 ng/mL. Median follow-up and rPFS were estimated using the Kaplan-Meier method. Results: Of 347 patients reviewed, 323 were included in the analysis after excluding 24 with irregular follow-up or incomplete PSA data. The median age was 68 (43–88) years, and the majority of patients (51.7%) had Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0. Of the patients, 50.5% had high-volume disease, and 76.5% had synchronous metastasis. Additionally, 76.5% of the patients had bone metastasis, 12.4% had lung metastasis, and 4.3% had liver metastasis. Treatment distribution among patients was as follows: 25.1% received ADT alone, 24.5% received ADT combined with docetaxel, and 50.5% received ARPIs in combination with ADT. Among patients receiving first-line therapy, 50 (15.5%) achieved ultra-low PSA levels (<0.02 ng/mL), 60 (18.9%) had PSA levels of 0.02–0.2 ng/mL, and 212 (65.6%) had PSA levels >0.2 ng/mL during the first three months of treatment. Within the first three months, ultra-low PSA levels were achieved in 12.4% of patients receiving ADT alone, 7.6% of those receiving ADT plus docetaxel, and 20.9% of those receiving ARPIs plus ADT. The median rPFS was 34.2 months (95% CI, 27–40 months). The 5-year rPFS rates were 89% for patients with PSA <0.02 ng/mL, 80% for PSA 0.02–0.2 ng/mL, and 18% for PSA ≥0.2 ng/mL (p < 0.001). Conclusions: Early ultra-low PSA (<0.02 ng/mL within the first three months) is associated with longer rPFS in patients with mHSPC and may serve as a novel surrogate endpoint in future clinical trials.

Integrating Antiferromagnetic/Ferromagnetic Heterojunction in Van Der Waals Fe ₁₊ <i> _y </i> Te Film With Gradient Fe Doping

ABSTRACT Manipulating heterojunction architecture in van der Waals (vdW) magnets plays a significant role in developing exotic low‐dimensional spintronic physics and technological innovations in quantum computing. However, the conventional heterostructure strategy to engineer a vdW device through complicated and cumbersome stacking strategies is facing a high fabrication cost. Tailoring broken time‐reversal symmetries to integrate a distinct magnetic order into a vdW system, by only employing a simplified geometry and the advantage of unique components, currently remains highly challenging. In this work we propose the use of a gradient doping of magnetic atoms in bicollinear antiferromagnetic (AFM) parent vdW magnet to fabricate an AFM/ferromagnetic (FM) heterojunction in a single Fe 1+ y Te film, which enables an exchange bias (EB) effect. We demonstrate the emergence of robust FM order and an EB effect in a vdW Fe 1+y Te film. This originates from heavy Fe doping in the interfacial layers and the breaking of symmetry in the bicollinear AFM order within the lightly doped layers away from the interface. This work not only opens a new avenue for manipulating AFM/FM heterojunction in a single parent vdW system but also provides new insights into understanding the production of the EB effect on the bicollinear AFM vdW device platform.

Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

Healthcare utilization and expenditure burden in bladder cancer: A nationally representative analysis (MEPS 2015–2022).

645 Background: Bladder Cancer (BCa) is recognized as a high-cost malignancy, largely from chronic disease course, recurrence, and intensive follow-up. However, data on healthcare utilization (HCU) and expenditures (exp), including out-of-pocket (OOP) costs, remain limited. We compared HCU and costs across BCa, other cancers, and non-cancer groups. Methods: A repeated cross-sectional study using the Medical Expenditure Panel Survey (2015–2022) categorized respondents as BCa, non-BCa cancers (prostate, colorectal, lung, melanoma, lymphoma, breast, gynecologic), or no cancer history. Outcomes included annual healthcare utilization (HCU)—emergency, outpatient, inpatient, and prescription visits per person per year, and expenditures (total and out-of-pocket), inflation-adjusted to 2020 USD. Survey-weighted regression estimated incidence rate ratios (IRRs, 95% CIs), adjusting for demographic, sociodemographic, functional, and clinical covariates. Results: Among 165,665 respondent-years (85,194 individuals; mean age 55.7 years), 0.2% had bladder cancer (BCa), 4.5% other cancers, and 95.3% no cancer. BCa patients had the highest healthcare utilization (38.9 ± 33.3 physician interactions; 0.44 ± 0.86 emergency visits per year), followed by non-BCa cancers (38.2 ± 36.6) and no-cancer respondents (14.8 ± 26.3; p&lt;0.001). In adjusted analyses, overall utilization was similar for BCa and other cancers (IRR 0.98, 95% CI 0.83–1.16) but lower for those without cancer (IRR 0.81, 0.69–0.97). Non-BCa cancers had fewer emergency (IRR 0.68, 0.49–0.94) and inpatient visits (IRR 0.71, 0.53–0.95), while outpatient and prescription use were comparable. Mean annual total expenditures were $15,537 (BCa), $16,305 (non-BCa), and $4,201 (no cancer; p&lt;0.001); adjusted total spending was similar for BCa and other cancers (IRR 0.98, 0.69–1.30) but lower for no cancer (IRR 0.64, 0.53–0.77). Out-of-pocket costs averaged $1,320 (BCa), $1,518 (non-BCa), and $509 (no cancer; p&lt;0.001). Conclusions: BCa patients had greater emergency and inpatient utilization than both non-cancer and other cancer respondents. Interestingly, despite higher service use, their total and OOP expenditures were comparable to those of other malignancies. Healthcare utilization and expenditure ratios (ref: bladder cancer). Outcome Category Outcome No History of Cancer, IRR (95% CI) Non-Bladder Cancer, IRR (95% CI) Utilization Total interactions 0.81 (0.69–0.97)* 0.98 (0.83–1.16) Emergency visits 0.52 (0.38–0.72)* 0.68 (0.49–0.94)* Outpatient visits 0.69 (0.59–0.81)* 0.92 (0.78–1.08) Inpatient visits 0.49 (0.37–0.65)* 0.71 (0.53–0.95)* Prescriptions filled 0.90 (0.74–1.09) 1.01 (0.83–1.23) Expenditures Total healthcare 0.64 (0.53–0.77)* 0.98 (0.69–1.30) Out-of-pocket 0.93 (0.70–1.23) 1.14 (0.85–1.53) *p&lt;0.05.

Use of active surveillance in young men with low-risk prostate cancer.

404 Background: Prostate cancer is the second most common cancer in men. The adoption of prostate specific antigen (PSA) screening has led to earlier diagnoses in more localized stages. With radical therapy for low-risk disease often being associated with long term morbidities without clear survival benefit, active surveillance has emerged as a safe strategy with level 1 evidence showing comparable outcomes to surgery or radiation. Despite guidelines recommending active surveillance as the management strategy of choice, recent literature suggests that younger individuals with low-risk prostate cancer still pursue treatment. As such, the goal of this study is to use the National Cancer Database (NCDB) to understand recent trends in active surveillance use among younger men with low risk, localized prostate cancer. Methods: We performed a retrospective study using the NCDB database from 2018-2022 to identify individuals diagnosed with NCCN low risk or very low risk prostate cancer and evaluated treatment strategies based on age quartile. Treatment strategies were defined as partial/complete prostatectomy or entire/partial prostate radiation, and no treatment. Other measured values included PSA, Gleason grade clinical, number of positive biopsy cores, and &gt;50% total cores positive. Results: A total of 103,596 men were included in this analysis. Treatment was pursued in 45.45%, 39.41%, 37.06%, and 29.99% of men in age quartiles 1 (&lt; 59 years), 2 (60-65 years), 3 (66-71 years), and 4 (&gt; 71 years), respectively (Table 1). Chi-square test showed significant differences between the quartiles (p&lt;0.00001). Additionally, multivariable logistic regression analysis including age, Gleason grade clinical, PSA, number of positive cores, and &gt;50% total positive cores, demonstrated that age was an independent predictor of receiving treatment (p&lt;0.001). Conclusions: In this retrospective analysis of the NCDB, young men with NCCN low/very low risk prostate cancer had high rates of definitive treatment. A young age of diagnosis was independently associated with the likelihood of receiving definitive treatment irrespective of other clinicopathologic factors, suggesting that active surveillance is underutilized in young men with localized, low risk disease. The NCCN low/very low-risk group’s active surveillance, treatment, and no treatment distribution. Low-Risk Quartiles 18-59 60-65 66-71 72-90 Total Active Surveillance 12974 14822 14926 8292 51014 Surgery 9712 7548 6248 3859 27367 Radiation 2656 3446 3843 2517 12462 No Treatment 1548 1731 1838 6394 11511 Unknown 323 348 376 195 1242

Dynamic analysis and structural parameters optimization of reciprocating double-action cutter for ramie based on FEM

Post-operative pelvic lymph node radiation therapy in lymph node positive prostate cancer and mortality risk.

117 Background: Whether including pelvic lymph nodes in post-radical prostatectomy (RP) radiotherapy (RT) volume for patients with pathologically node-positive (pN1) prostate cancer (PC) reduces mortality is unknown and was investigated. Methods: Multivariable Cox regression was used to evaluate whether a significant association existed between all-cause mortality (ACM)-risk and time-dependent use of whole pelvic lymph node RT (WPRT) plus prostate bed RT (PBRT) versus PBRT alone among the 816 patients with pT2-4pN1M0 PC treated with RP of which 48.65% had prostatectomy (p)Gleason score 8-10, after adjusting for age at and year of RT delivery, pre-RT PSA level, pGleason score, pTumor stage surgical margin status, number of removed and positive pelvic lymph nodes, and time-dependent use of androgen deprivation therapy. Both fixed and time-dependent covariates adjusted estimates of ACM were generated using the extended Kaplan–Meier method. Results: After a median follow-up of 4.83 years (Interquartile range: 3.84-5.90), of the 816 patients in the study cohort, 119 (14.58%) died, including 58 (48.74%) were from PC. The addition of WPRT to the post-operative RT treatment volume was associated with a significantly reduced ACM-risk compared with PBRT alone (adjusted HR, 0.31; 95% CI, 0.18 to 0.55; P &lt; .001). Conclusions: WPRT has the potential to reduce mortality-risk in patients with pN1 PC.

A Wireless, Bioresorbable Postoperative Treatment System with Temperature Feedback, Photothermal, and Drug Combination Therapy

ABSTRACT Postoperative tumor recurrence remains a significant challenge for the long‐term survival of patients. Although synergistic combination therapies involving photothermal therapy and local chemotherapy show considerable promise, critical obstacles remain to clinical translation, such as insufficient temperature monitoring and the difficulty in integrating multiple therapeutic functions. Herein, we report a wireless, bioresorbable postoperative treatment system that integrates temperature feedback, photothermal therapy, and on‐demand drug release within a single implantable platform. An asymmetrically interconnected inductive‐capacitive (LC) sensor layout enables in situ, real‐time temperature monitoring via inductive coupling, while a photothermal patch provides localized heating and controlled drug release. In vitro and in vivo studies, such as the S180 tumor model, demonstrate effective thermal control, stable wireless operation, and enhanced therapeutic efficacy. The device can be implanted after tumor resection surgery to perform its therapeutic functions, and subsequently degrade and be absorbed by the body, providing a multifunctional and clinically compatible strategy for postoperative tumor management.