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Glutathione-Mediated Biomimetic NO Activation with Coordination Capsules for NH ₃ and α-Amino Acid Electrosynthesis

An adversarial-resilient intrusion detection framework for internet of medical things (IoMT) using digital twin-enabled behavioral threat modeling and federated hybrid ensemble learning

Concurrent thoracic radiotherapy (TRT), platinum/etoposide chemotherapy, and durvalumab immunotherapy in extensive-stage (ES) small cell lung cancer (SCLC): A phase III trial.

LBA8005 Background: A phase III trial indicated a survival benefit of TRT after chemotherapy in ES SCLC. A synergistic effect of concurrent radiotherapy and immunotherapy has been proposed and retrospective studies suggest that TRT improves survival in ES SCLC patients receiving chemoimmunotherapy (chemo-ICI). The main aim of this phase III trial was to investigate whether adding TRT to chemo-ICI improves overall survival (OS) in ES SCLC. Methods: Eligible patients were ≥18 years, had ECOG performance status (PS) 0-1 and disease stage III-IV (TNM 8) ineligible for curative chemoradiotherapy and were randomized 1:1 to chemo-ICI plus TRT («TRT») or chemo-ICI alone («C-I»), stratified by presence of liver and brain metastases. Patients received 4 courses of carboplatin (AUC 5), etoposide (100 mg/m 2 iv day 1-3 or 100 mg/m 2 iv day 1 plus 200 mg/m 2 po days 2-4) and durvalumab 1500 mg q3w, followed by durvalumab 1500 mg q4w until progression, unacceptable toxicity or patients wished to discontinue. TRT of 30 Gy/10 fractions to thoracic lesions started 21-28 days after day 1 of the 1st chemo-ICI cycle. Prophylactic cranial irradiation of 25-30 Gy/10-15 fractions was considered for those responding to chemo-ICI. Primary endpoint was OS, secondary endpoints include overall response rates (ORR), progression free survival (PFS) and toxicity. To show an increase in 1-year survival rates from 53% to 66% with a 2-tailed α of 0.05 and a β of 0.20, 128 patients were required in each group. Results: Enrolment started in January 2022 and was prematurely discontinued in September 2025 according to recommendations by the independent Data and Safety Monitoring Committee due to more serious adverse events (AE) in the TRT group and futility. By then, 228 patients from 20 European hospitals were randomized (TRT: n =115, C-I: n =113). Median age was 68 (range 39-84), 50.4% were female, 37.7% had PS 0, 96.1% stage IV disease, 39.9% metastases to the liver and 28.1% to the brain. Treatment groups were well balanced. Mean number of chemo-ICI courses was 3.6, mean number of total durvalumab courses 7.5 (range 1-30) and 91.3% in the TRT group received TRT. TRT did not improve OS (median 10.0 [TRT] vs. 11.1 months, HR 1.12, 95% CI 0.82-1.54, p=0.47), ORR (TRT: 88.5%, C-I: 89.6%, p=0.79) or PFS (median 5.1 [TRT] vs. 5.1 months, HR 1.09, 95% CI 0.83-1.44, p=0.53). Overall, there were more AEs in the TRT group (87.8% vs. 69.9%, p=0.006), but not more grade 3-4 AEs (TRT: 21.1%, C-I: 17.5%, p=0.33). Esophagitis occurred in 47.8% and grade 3-4 esophagitis in 10.4% of the TRT group. There were more deaths from other causes than SCLC in the TRT group (14.8% vs. 3.5%, p=0.003), though not significantly more when excluding deaths occuring before TRT commenced (9.6% vs. 3.5%, p=0.067). Conclusion: The addition of TRT after the first cycle of chemo-ICI did not improve treatment outcomes in ES SCLC. Clinical trial information: NCT05223647 .

Unraveling the Electrochemical Mechanism of Cobalt Phthalocyanine for CO ₂ and CO Reduction under Heterogenized Conditions

Preoperative prediction of pathological pelvic lymph node metastasis in prostate cancer using an elastic net model integrating clinicopathologic and 68Ga-PSMA PET/CT features: development and temporal validation

Event-free survival with adjuvant selpercatinib in stage IB-IIIA <i>RET</i> fusion-positive NSCLC: Primary results of the phase 3 LIBRETTO-432 trial.

LBA3 Background: Selpercatinib, a highly selective, potent and brain-penetrant RET inhibitor, is approved for RET fusion-positive ( RET+ ) advanced/metastatic non-small cell lung cancer (NSCLC). RET-directed therapy has yet to be examined in patients (pts) with stage IB-IIIA RET+ NSCLC, where recurrence rates after definitive therapy remain high, and no adjuvant targeted therapy is approved. Here, we report the efficacy and safety of selpercatinib vs placebo in this population. Methods: LIBRETTO-432 (NCT04819100) is a placebo-controlled, double-blind, phase 3 randomized (1:1) trial of selpercatinib 160mg BID vs placebo for up to 3 years in pts with stage IB-IIIA RET+ NSCLC after definitive locoregional treatment. Primary endpoint was investigator-assessed event-free survival (EFS) in stage II-IIIA pts. Secondary endpoints were investigator-assessed EFS in all randomized pts (overall population, stage IB-IIIA), EFS by blinded independent central review (BICR), overall survival and safety. Crossover from placebo to selpercatinib was allowed upon disease recurrence. Results: In total, 151 pts were randomized (selpercatinib n=75; placebo n=76) and baseline characteristics were balanced across treatment arms. Median follow-up was 24 months for selpercatinib and 27 months for placebo. At the preplanned efficacy analysis, selpercatinib demonstrated significantly improved EFS in pts with stage II-IIIA disease (n=109), HR 0.172 (95% CI: 0.058, 0.509; p=0.0003). The median EFS was not reached for selpercatinib vs 31.8 months for placebo (4 vs 19 EFS events, respectively). EFS by BICR, HR=0.125 (95% CI: 0.028, 0.552; p=0.0011), was consistent with investigator-assessed EFS. The 2-year EFS rate was 91.5% for selpercatinib vs 61.1% for placebo. In the overall population (n=151), error-controlled EFS HR was 0.165 (95% CI: 0.056, 0.485; p=0.0002), and median EFS was not reached on either treatment arm. Adverse events (AEs) with selpercatinib were comparable to those reported in metastatic RET + NSCLC. The most common AEs were increased ALT/AST. Only 3 deaths were observed, all occurred in the placebo arm due to the study disease. No pts died during assigned study treatment. Conclusions: Selpercatinib achieved a statistically significant and clinically meaningful improvement in event-free survival compared to placebo in patients with early-stage RET+ NSCLC. These data add to the body of evidence for targeted therapy, including EGFR and ALK inhibitors, in the adjuvant NSCLC setting and underscore the importance of comprehensive genomic testing at diagnosis of NSCLC across disease stages to inform optimal therapeutic decision-making. Clinical trial information: NCT04819100 .

Aqueous-Based Biomimetic Porphyrin-Catalyzed Surface Oxidation of Polyethylenes for Enhanced 3D-Printability

Reduced sensitivity to tactile stimuli associated with physical and mental disorders: A monozygotic twin study

Abstract Tactile sensitivity is crucial for perceiving subtle external stimuli and maintaining a high quality of life. While individual differences in tactile sensitivity are influenced by local factors, such as skin condition and nerve density, the relationships between tactile sensitivity and systemic factors, such as physical and mental health, remain unclear. This study investigated how systemic conditions are related to tactile sensitivity, excluding genetic influences, by analyzing 25 pairs of monozygotic (MZ) twins. Tactile thresholds were measured using suction stimuli on the cheek and compared with psychophysiological data from questionnaires and objective measurements. The results revealed that 18 twin pairs presented similar thresholds, indicating a genetic influence. However, in 7 twin pairs with differing thresholds, reduced tactile sensitivity was associated with greater physical and mental disorders, such as fatigue and anxiety. These findings suggest that tactile sensitivity is influenced not only by genetic factors but also by systemic health conditions that are shaped by lifestyle. Furthermore, impaired tactile sensitivity may reflect broader physical and mental health issues, making it a potential marker for preventive health interventions. This study provides insights into the complex interplay between tactile perception and systemic health, paving the way for tactile interventions aimed at enhancing the quality of life.

Ultra-low-dose immunotherapy plus oral metronomic chemotherapy versus paclitaxel-carboplatin in platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma: A randomized phase III trial.

LBA6007 Background: Standard first-line therapy for recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) includes platinum-based chemotherapy (PBC) combined with pembrolizumab or cetuximab; however, these regimens remain inaccessible for many patients globally, particularly in resource-limited settings. Triple oral metronomic chemotherapy combined with ultra-low-dose immunotherapy (TMC-I) has demonstrated promising activity and tolerability in earlier studies. We conducted a randomized phase III trial comparing TMC-I with PBC (paclitaxel and carboplatin) in patients with R/M-HNSCC receiving first-line palliative therapy. Methods: In this open-label, multicenter, phase III trial conducted at two centers, 422 patients with R/M-HNSCC were randomized (1:1) to receive paclitaxel 175 mg/m² plus carboplatin AUC 6 every 3 weeks (Arm-A) or TMC-I (oral methotrexate 9 mg/m² weekly, celecoxib 200 mg twice daily, erlotinib 150 mg daily, and nivolumab 20 mg IV every 3 weeks) (Arm-B). Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and quality of life (QoL). The planned sample size of 422 patients (211 per arm) provided 80% power with a two-sided α of 0.05. The trial was registered with the Clinical Trials Registry–India (CTRI/2024/01/061661). Results: The median age was 49.5 years (IQR 42–58), 85.5% were male, 78.9% had oral tobacco use, 76.3% had oral cavity primaries, 25.6% had metastatic disease, and 30.6% had ECOG performance status 2. After a median follow-up of 10.8 months (95% CI 8.1–13.6) in Arm-A and 11.9 months (95% CI 10.3–13.4) in Arm-B, the primary endpoint of OS was significantly improved with TMC-I compared with PBC. Twelve-month OS was 46% versus 23%, and six-month OS was 69% versus 52% (p &lt; 0.001). Median OS was 10.3 versus 6.2 months (HR 0.565, 95% CI 0.439–0.728; p &lt; 0.001). Median PFS was 5.5 versus 2.7 months (HR 0.465, 95% CI 0.371–0.582; p &lt; 0.001). ORR was higher with TMC-I than with PBC (53.4% vs 24.1%; p &lt; 0.001), with fewer grade ≥3 adverse events (34.1% vs 46.4%; p = 0.010). No treatment-related deaths were observed, and patient-reported QoL was preserved with TMC-I. Conclusion: TMC-I significantly improved survival outcomes and response rates while reducing severe toxicity and preserving QoL compared with PBC. At approximately USD 230 per month, TMC-I represents a promising and cost-effective first-line treatment option for patients with R/M-HNSCC. Clinical trial information: CTRI/2024/01/061661.

Insights into the Debated Lyase Mechanism of Bifunctional DNA Glycosylases from MD and QM/MM MD Simulations: The Case Study of DNA Oxidative Damage Repair by Human 8-Oxoguanine DNA Glycosylase

The integrated to developmental stress response (ISR-DASR) shift reveals a functional transition from cellular to stem cell organismal adaptation

Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non–small cell lung cancer: Overall survival results of the phase 3 HARMONi-6 trial.

LBA4 Background: In the prespecified interim analysis of progression-free survival (PFS) from the HARMONi-6 study, ivonescimab combined with chemotherapy significantly improved PFS compared with tislelizumab plus chemotherapy in patients with previously untreated advanced squamous NSCLC(sq-NSCLC). Here we report the results of the prespecified overall survival (OS) analysis. Methods: Patients with previously untreated stage III-IV sq-NSCLC were randomly assigned (1:1) to receive ivonescimab 20 mg/kg every 3 weeks (Q3W) or tislelizumab 200 mg Q3W, each in combination with paclitaxel (175 mg/m²) and carboplatin (AUC 5) for 4 cycles, followed by maintenance ivonescimab or tislelizumab monotherapy. Randomization was stratified by disease stage (IIIB/IIIC versus IV) and PD-L1 tumor proportion score (TPS; ≥1% versus &lt;1%). The primary endpoint was PFS assessed by independent radiographic review committee per RECIST v1.1. OS was a key secondary endpoint and was hierarchically tested using a closed sequential testing procedure. PFS was tested first at one-sided α level of 0.025, OS was tested at the same α only after statistical significance for PFS was established. This analysis represents the first planned OS analysis with an efficacy boundary of one-sided P=0.0049. Results: A total of 532 patients were randomly assigned (n=266 per arm). As of February 27, 2026, at a median follow-up of 21.4 months, ivonescimab plus chemotherapy significantly improved OS compared with tislelizumab plus chemotherapy. Median OS was 27.9 months (95% CI, 27.89 to NE) with ivonescimab plus chemotherapy versus 23.7 months (95% CI, 20.11 to NE) with tislelizumab plus chemotherapy (hazard ratio [HR], 0.66; 95% CI, 0.50 to 0.87; one-sided P =0.0017), meeting the prespecified boundary (P&lt;0.0049) for statistical significance.The OS benefit was consistent across prespecified subgroups. Among patients with PD-L1 TPS &lt;1%, median OS was NE versus 18.6 months (HR, 0.64; 95% CI, 0.43 to 0.96). Among patients with PD-L1 TPS≥1%, median OS was NE versus 27.3 months (HR, 0.68; 95% CI, 0.46 to 0.99). The safety profile of ivonescimab plus chemotherapy was manageable and consistent with prior reports, with no new safety signals observed. Conclusion: Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared with tislelizumab plus chemotherapy in previously untreated patients with advanced sq-NSCLC. Notably, ivonescimab plus chemotherapy is the first regimen to show clinical superiority over an active PD-1 inhibitor control arm in the first-line setting. The dual-targeted approach of ivonescimab delivers improved survival outcomes with a favorable risk-benefit profile, establishing a compelling new standard of care in the management of advanced sq-NSCLC. Clinical trial information: NCT05840016 .

Structural and Spectroscopic Basis for Catalysis by a Class C Radical <i>S</i> -Adenosylmethionine Methylase Involved in Nosiheptide/Nocathiacin Biosynthesis

Complete mitochondrial genome sequence of Koelreuteria paniculata (Sapindaceae) and comparative analysis within the family Sapindaceae

Adjuvant aspirin for stage III colorectal cancer after curative resection: Primary analysis of the randomized double-blind placebo-controlled phase III trial (EPISODE-III: JCOG1503C).

LBA3508 Background: Observational studies suggest aspirin benefits in colorectal cancer (CRC), but adjuvant evidence remains limited. In unselected populations, phase III trials have not shown a clear benefit, while biomarker-selected studies suggest a benefit in PI3K-altered tumors. EPISODE-III evaluates whether low-dose aspirin improves disease-free survival (DFS) in unselected stage III CRC receiving standard adjuvant chemotherapy. Methods: EPISODE-III is a multi-institutional, two-arm, randomized, double-blind, placebo-controlled phase III trial at 36 institutions in Japan. Eligible patients (20–80 years; ECOG PS 0–1) with histologically confirmed, R0-resected stage III adenocarcinoma from the cecum to upper rectum (lower rectum excluded) after D2/D3 lymph node dissection were randomized 1:1 to low-dose aspirin (100 mg once daily) or matched placebo for 3 years, in addition to standard adjuvant chemotherapy (capecitabine, mFOLFOX6, or CAPOX). Randomization was balanced by institution, sex, stage (IIIA/IIIB/IIIC), and planned oxaliplatin use. The primary endpoint was DFS (event: relapse, second cancer, or death). Secondary endpoints included overall survival (OS), relapse-free survival (RFS), relative dose intensity (RDI) of aspirin and placebo, and safety. The planned sample size was 880 (279 DFS events), providing 80% power with a one-sided α = 0.05 to detect hazard ratio (HR) of 0.741 (assumed 3-year DFS 74% vs. 80%). Results: Between Mar 2018 and Oct 2022, 882 patients (placebo 442; aspirin 440) were enrolled. At the data cutoff (Oct 2025), the median follow-up for all randomized patients was 4.0 years, with 231 DFS events (placebo 124; aspirin 107). Baseline characteristics were balanced (median age 65 vs. 64 years; pIIIA/IIIB/IIIC 19/63/18% vs. 19/62/19%; planned oxaliplatin-containing regimen 70% vs. 71%). Three-year DFS was 75.4% with placebo and 78.8% with aspirin (+3.4%); the primary endpoint was not met (HR 0.84, 95% CI 0.65–1.09; one-sided p=0.0987). DFS, RFS, and OS are shown in the Table. Grade ≥3 adverse events were similar between arms, and grade ≥3 aspirin-related adverse events were &lt;1% (lower GI bleeding n=4). One treatment-related death was observed in the aspirin arm during chemotherapy (ischemic heart disease). RDI was high and comparable (median 98.6% in both arms). Conclusion: Low-dose aspirin added to standard adjuvant chemotherapy did not significantly improve DFS in unselected stage III CRC. However, a numerical DFS improvement with good tolerability was observed. Exploratory biomarker analyses including PI3K/PIK3CA are ongoing and will inform a planned collaborative meta-analysis of randomized trials. Clinical trial information: jRCTs031180009. 3-year (%)placebo vs. aspirin HR (95% CI) P (one-sided) DFS 75.4 vs. 78.8 0.84 (0.65–1.09) 0.0987 RFS 77.2 vs. 79.5 0.87 (0.66–1.14) - OS 96.6 vs. 95.2 1.02 (0.65–1.60) -

Pronounced Neuroplasticity in the Primary Visual Cortex of the 13-Lined Ground Squirrel during Hibernation

Hibernating animals can show neuroplasticity throughout the hibernation season. In ground squirrels, decreased dendritic arborization in the hippocampus, somatosensory cortex, and thalamus during deep hibernation (“torpor”) suggests that this neuroplasticity is a brain-wide phenomenon. However, the degree to which neuroplasticity occurs in the visual system is not clear. While transient retinal changes have been reported during torpor, neuroplasticity beyond the retina remains unknown. Here, we characterized hibernation-related neuroplasticity in the primary visual cortex (V1), the first cortical area to receive visual information, in the 13-lined ground squirrel ( Ictidomys tridecemlineatus ). We compared neuronal morphology in Golgi-stained samples from male and female hibernating or nonhibernating squirrels. For the hibernating squirrels, the brain tissue was sampled during two different epochs: torpor and intertorpor arousal. Dendritic arborization decreased during torpor in V1 layer 2/3 pyramidal neurons, manifesting as decreases in dendritic length, number, and complexity. These changes fully reversed during intertorpor arousal, indicating that on average dendritic arbors grew by 0.75 mm (65%) over ∼1.5 h. No morphological differences between hibernating and nonhibernating squirrels were apparent when compared 6 months after the hibernation season. We also found no neuroplastic changes in V1 layer 4 spiny stellate neurons, unlike in this cell type in the somatosensory cortex. Together, this revealed, for the first time, hibernation-related neuroplasticity in V1 in support of a brain-wide mechanism but with area-specific differences. The speed and magnitude of this naturally occurring neuroplasticity could make ground squirrel V1 a powerful translational model system for conditions requiring neuroplasticity, such as recovery from stroke.

In the wake of the Hayli Gubbi eruption

Anbenitamab plus albumin-bound docetaxel (nab-docetaxel) ± carboplatin (Cb) versus trastuzumab and pertuzumab plus docetaxel (THP) ± Cb as neoadjuvant therapy for HER2-positive early or locally advanced breast cancer: A randomized, open-label, multicenter, phase 3 trial.

LBA660 Background: THP ± Cb represent the standard neoadjuvant treatment for HER2-positive breast cancer. Despite achieving total pathological complete response (tpCR) rates between 39.3% and 56.0%, there remains a clinical need to further improve outcomes, as tpCR is strongly correlated with long-term survival. Anbenitamab (KN026) is a novel biparatopic antibody targeting HER2 domains II and IV. This phase 3 study (NCT06747338) compared the efficacy and safety of an Anbenitamab-based regimen to the standard-of-care THP± Cb regimen in the neoadjuvant setting. Methods: Patients with HER2-positive early or locally advanced breast cancer were randomized 1:1 to receive 6 cycles of either Anbenitamab plus nab-docetaxel ± Cb [Anbenitamab arm] or trastuzumab, pertuzumab, and docetaxel ± Cb [THP ± Cb arm]. Randomization was stratified by clinical stage, hormone receptor status, and planned carboplatin use. The primary endpoint was tpCR (ypT0/is, ypN0) as assessed by a Blinded Independent Review Committee (BIRC). Results: A total of 521 patients were randomized. The study met its primary endpoint, with a significantly higher tpCR rate in Anbenitamab arm compared to THP ± Cb arm (62.4% [95% CI: 56.2–68.2] vs. 51.2% [95% CI: 44.9–57.4]). The stratified difference in tpCR was 11.4% (95% CI: 3.2–19.6); one-sided P = 0.0036). Consistent results were observed for investigator assessed tpCR (63.9% [95% CI: 57.8–69.7] vs. 51.2% [95% CI: 44.9–57.4], one-sided P = 0.0011). Similar improvements in BIRC-tpCR were observed across all prespecified subgroups, including those defined by hormone receptor status, clinical stage, and planned carboplatin use. BIRC-assessed breast pCR was also significantly higher in Anbenitamab arm (64.6% vs 55.0%, one-sided P = 0.0099). The overall incidence of treatment emergent adverse events (TEAEs) was 98.5% in Anbenitamab arm versus 98.8% in THP ± Cb arm. Grade ≥3 TEAE rates were similar (29.3% vs 28.3%). Most common Grade ≥3 TEAEs were neutropenia (11.4 % vs 10.9%) and leukopenia (7.6% vs 8.5%). TEAEs leading to interruption of any study drug occurred in 5.7% vs 7.4% of patients. Permanent discontinuations due to TEAEs occurred in 4.9% vs 3.5% of patients. Safety profiles were primarily hematologic and gastrointestinal toxicities， consistent with known safety profiles of respective single agents, and no new safety signal was observed. Conclusions: Anbenitamab plus nab-docetaxel ± Cb significantly improved tpCR rate compared with standard of care as neoadjuvant therapy in patients with early or locally advanced HER2-positive breast cancer, with a manageable safety profile. These results support Anbenitamab-based regimen as a potential new standard of care. Clinical trial information: NCT06747338 .

Tracing the Origin of Driving Force of Photoinduced Interfacial Electron Transfer Reaction by Colocated Scanning Electrochemical Microscopy

Marker-trait association analysis revealed loci linked to salinity tolerance in a worldwide collection of safflower