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Ag-Doping-Mediated Interlayer Coordination Engineering: Enabling Thermoelectric <i>ZT</i> = 1 in TMDs-Derived Narrow-Gap Semiconductor CuCrTi ₂ Se ₆

Non-Equilibrium Growth Processes to Glyceraldehyde and Glycerol as Building Blocks of Interstellar Sugars and Phospholipids

Combined effects of tactile stimulation and aerobic exercise on BDNF-related pathways and neurofunctional outcomes in an early-stage 5xFAD mouse model of Alzheimer’s disease

Neoadjuvant intralesional daromun (L19IL2/L19TNF) in resectable locally advanced melanoma: An update on the primary outcome and sensitivity analyses (EFS) from the PIVOTAL phase 3 trial.

LBA9517 Background: PIVOTAL (NCT02938299) is an open-label, randomized, multicenter, phase 3 trial evaluating daromun as a neoadjuvant intralesional (IT) therapy for resectable, locally advanced stage III melanoma. The trial enrolled 256 efficacy-evaluable patients (pts) in the EU and met its primary endpoint, demonstrating a statistically significant improvement in recurrence-free survival (RFS; HR = 0.59; p = 0.005) for daromun versus upfront surgery, at a median follow-up (FU) of 21 months from randomization (Kähler et al, Ann Onc 2025, 36, 1166). Methods: Pts with skin and/or lymph node metastatic melanoma amenable to complete surgical resection were randomized (1:1) to receive 4 weekly IT injections of daromun (13 Mio IU of L19IL2 and 400 μg of L19TNF) followed by surgery or upfront surgery alone. Prior surgery, radiotherapy (RT) and/or systemic therapies (ST) were permitted, as well as any approved adjuvant treatment post-surgery.The primary endpoint was RFS, the secondary endpoints included DMFS, OS and safety. An event-free survival (EFS) sensitivity analysis was conducted, considering progression to unresectable melanoma before surgery, recurrence of the disease, or death due to melanoma or treatment as events. Results: An updated primary outcome analysis at a median FU of over 36 months from randomization (database cut-off Nov. 29, 2025) confirmed a clinically relevant improvement in RFS (HR = 0.60; p = 0.003) for daromun versus upfront surgery. The EFS sensitivity analysis carried out in the overall population was consistent with the RFS results (HR = 0.66; 95% CI = 0.47-0.92).The PIVOTAL trial included two clinically distinct subgroups: pts with newly diagnosed disease (n = 32; 12%) and pts with recurrence(s) after surgery and/or systemic (neo)adjuvant treatment (n = 224; 88%). Among the recurrent cohort, 86 pts (38.3%) had received and failed previous ST, while 138 pts (61.6%) had only received surgery/RT. Sensitivity EFS analyses were also performed in i) the recurrent cohort (HR = 0.59; 95% CI = 0.41-0.85), ii) the subgroup of pts in the recurrent cohort who had only received previous surgeries and/or RT (HR = 0.55; 95% CI = 0.34-0.89), and iii) the pts subgroup in the recurrent cohort who received prior ST (HR = 0.63; 95% CI = 0.36-1.08 ). The rate and type of treatment-related adverse events at a longer FU were consistent with previous reports, and no new safety risks were identified. Conclusions: With longer FU the highly significant reduction in the risk of recurrence or death with neoadjuvant daromun in pts with locally advanced stage III melanoma is confirmed. The sensitivity EFS analyses provide consistent, confirmatory evidence of daromun’s efficacy across the entire trial population and, more importantly, in the subgroup of pts with recurrent disease, regardless of any prior ST. No new safety signals were reported. Clinical trial information: NCT02938299 .

Cortical reinstatement of causally related events sparks narrative insights by updating neural representation patterns

In Vivo Imaging of a Photoactivatable Platinum Prodrug by Metal-Centered Radiolabeling

Employing molecular beacons to assess in vitro transcription with single-molecule resolution

Abstract Transcription is a vital cellular process in which RNA polymerase produces messenger RNAs (mRNA) from a DNA template. Many transcription systems have been developed to reproduce this process in vitro and in the confined environment of giant unilamellar vesicles (GUVs). However, these systems and the studies employing them often use DNA concentrations significantly higher than those found in natural cells, which typically contain a single DNA copy. In this work, we introduce single-molecule in vitro transcription (smIVT) that overcomes this limitation, enabling the visualization and tracking of individual mRNA molecules both in solution and within GUVs. We achieved this by employing a molecular beacon—a quenched RNA or DNA hairpin probe that becomes fluorescent after binding to the transcript mRNA—and template DNA encoding 32 repeats of the molecular beacon binding sequence. With these, we ensured a signal-to-noise ratio sufficient to detect single mRNAs. We use smIVT to compare the performance of various commercially-available in vitro transcription kits, and to quantitatively describe single molecule transcription inside GUVs. We establish smIVT as a remarkable technique for scrutinizing in vitro transcription with single-molecule resolution.

Updated outcomes from STAMP: Surgically treated adjuvant Merkel cell carcinoma with pembrolizumab, a phase III trial—ECOG-ACRIN EA6174.

LBA9505 Background: EA6174 (STAMP) is the first randomized phase III trial of adjuvant pembrolizumab (pembro) in resected Merkel cell carcinoma (MCC), a rare, aggressive skin cancer with high relapse risk after surgery. This abstract presents new analyses of MCC-specific outcomes and radiation therapy (RT) effects. Methods: Patients (pts) with resected stage I without a sentinel lymph node biopsy to IIIB MCC were randomized 1:1 to pembro 200 mg IV q3 weeks ×17 doses (n = 147) or standard of care (SOC) (n = 146). Randomization was stratified by stage (I/II vs III) and intended RT. Co-primary endpoints were relapse-free survival (RFS) and overall survival (OS). MCC-specific outcomes were captured as relapse due to recurrence or death due to any cause (RFS_a), and MCC-specific recurrence and death (RFS_b). Distant metastasis-free survival (DMFS) was defined as time to distant recurrence or death from MCC. 280 pts provided 80% power with one-sided type 1 error rate of 0.05 to evaluate the hazard ratio (HR) of 0.56 hierarchically (RFS before OS). One-sided p-values from the log-rank test are reported in the analysis (data as of 2/19/26, median follow-up 47 months). Results: 293 pts enrolled (67.9% male; 84.3% stage III, median age 69, &gt; 50% accrued during the COVID-19 pandemic). Overall RFS (RFS_a) was numerically improved with pembro but not statistically significant between arms (p = 0.10). DMFS was improved in pts treated with pembro (p = .05). Significant improvement was observed in MCC-specific outcomes (RFS_b) in pts treated with pembro, with HR = 0.66 [90%CI (0.45,0.96)], resulting in 1-year and 2-year RFS_b rates of 84% [90%CI(78,88)] and 77% [90%CI(70,82)] in the pembro arm, compared with 73% [90%CI( 67,79)] and 67% [90%CI (60,74)], in the SOC arm (p = 0.032). The impact of pembro on RFS_b was maintained (p = 0.039) among the subset that received any RT (n = 131 pembro, n = 123 SOC). For pts treated concurrently with RT, pembro did not affect outcomes; however, for pts treated sequentially with RT prior to randomization (n = 68 pembro and n = 65 SOC), pembro improved RFS_a (P = 0.014), RFS_b (p = 0.009), and DMFS (p = 0.004). Conclusions: EA6174 demonstrates that pts treated with pembro experienced significantly fewer MCC-related events than pts who received SOC and that adjuvant pembro improves DMFS. RFSa may have been influenced by the average age of enrolled pts and by disruptions and morbidity associated with patient enrollment during the COVID-19 pandemic; as such RFSb may be a more accurate indicator of pembro efficacy. These findings support a meaningful impact of pembro on MCC-specific outcomes, particularly for distant relapse. Pembro may be of particular benefit when RT is delivered sequentially rather than concurrently with pembro, similar to other studies of RT and immunotherapy in solid tumors. Mature OS and MCC-specific survival data will further guide use of adjuvant immunotherapy for MCC. Clinical trial information: NCT03712605 .

Single-atom photocatalyst for click reaction

Abstract Copper(I)-catalyzed azide-alkyne cycloaddition is the most prevalent click chemistry reaction, which is widely exploited for the synthesis of diverse organic molecules. Typically, the Cu(I) catalysts are generated in situ through the chemical reduction of Cu(II) ions. Unfortunately, such homogeneous systems are considered impractical for large-scale production, and the involvement of multiple equilibria among catalysts, reductants, and substrates complicates elucidation of the catalytic process. Inspired by photosynthesis, which involves transient redox cycle of magnesium porphyrin moiety in chlorophylls, a metal complex-based strategy is proposed for light-triggered click chemistry reactions, utilizing a single-atom Cu(II)-loaded covalent organic framework as a heterogeneous catalyst, wherein the organic ligand functions as a robust scaffold and photoinitiator. Upon light irradiation, photogenerated electrons within the ligand moiety undergo ligand-to-metal charge transfer, injecting into the 3  d orbital of Cu(II) and reducing it to Cu(I) as a short-lived transient species with submicrosecond lifetime, which acts as efficient active sites for the click chemistry reaction. This controllable and robust system shows promise in photochemical cycloaddition of benzylazide and phenylacetylene, a model click chemistry reaction, achieving 95% substrate conversion and &gt;90% triazole yield. The findings are anticipated to be broadly applicable in areas such as sustainable photolithography and polymer chemistry.

Photochemical Deracemization of Aza-1-isoindolinones: Critical Influence of Catalyst Substitution and the Nature of Its Resting State

Clinical application of AI for lung lobe segmentation and functional quantification with SPECT/CT: open-source versus custom models

Erratum: Lenalidomide Plus Rituximab for Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 5-Year Follow-Up and Subgroup Analyses From the Phase III AUGMENT Trial

Jet-induced rainfall seasonality and C4 migration over East Asia

Abstract The Neogene expansion of C 4 grasslands transformed terrestrial ecosystems with marked influence on mammalian evolution, including hominins. However, the asynchronous C 4 expansion on different continents makes it difficult to identify the environmental drivers, especially for higher latitudes. Here we show that rainfall seasonality governed extratropical Plio-Pleistocene C 4 distributions in East Asia. Rainfall oxygen isotope ratios and clumped isotope soil temperatures exhibit coupled variations on the Chinese Loess Plateau (CLP) from 7 to 2.5 million years ago, indicating more spring rain during warmer times when the subtropical westerly jet was further poleward, and more concentrated summer rain under cooler climates. We attribute these changes to meridional shifts of a summer rain band on orbital and longer timescales. The most C 4 -rich ecosystems, as identified by organic carbon δ 13 C records, tracked this summer rain band, eventually eclipsing the southern CLP margin during the late Pleistocene cooling. Our model refines the East Asian paleomonsoon concept and explains the equatorward migration of extratropical C 4 ecosystems, highlighting the tight coupling between regional rainfall seasonality and vegetation.

Iron(IV)–Cyanide Complexes Capable of Asynchronous Basicity-Driven PCET in C–H Activation upon Linkage Isomerization

Edge AI enabled MIMO MC-CDMA for 6G optimizing spectrum and energy efficiency with SIC and deep reinforcement learning

A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2−/ <i>PIK3CA</i> -mutant (MT) advanced breast cancer (VIKTORIA-1 Study 2).

LBA1008 Background: Current standard treatment (tx) for patients (pts) with HR+/HER2-/ PIK3CA -MT advanced breast cancer (ABC) includes selective inhibitors of the PI3K/AKT/mTOR (PAM) pathway, which induce class-effect toxicities (e.g., hyperglycemia, diarrhea). Gedatolisib (geda) is a highly potent, IV-administered, comprehensive inhibitor of the PAM pathway that targets all class I PI3K isoforms, mTORC1, and mTORC2. Geda has superior preclinical potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus and demonstrated activity in PIK3CA- MT and wild-type (WT) breast cancer cell lines. The randomized, open-label phase 3 VIKTORIA-1 clinical trial evaluated, in 2 cohorts by PIK3CA status, geda regimens in HR+/HER2- ABC that progressed during/after CDK4/6i + aromatase inhibitor (AI). In the PIK3CA -WT cohort, geda/fulv +/- palbo significantly improved PFS (HR vs. fulv, 0.24; 95% CI, 0.17-0.35; P&lt;0.001, and 0.33; 95% CI, 0.24-0.48; P&lt;0.001, respectively). We now present primary findings of the PIK3CA -MT cohort. Methods: Eligible pts had HR+/HER2- ABC with prior CDK4/6i + AI, no chemotherapy for advanced disease, no prior PAMi, measurable disease (RECIST v1.1), and HbA1c &lt;6.5%. Pts with PIK3CA -MT disease were randomized 3:3:1 to geda/palbo/fulvestrant, alpelisib/fulv or geda/fulv in 28-day cycles of geda 180 mg IV weekly for 3 weeks on/1 week off; palbo 125 mg daily for 21 days with 7 days off; fulv 500 mg IM every 2 weeks in cycle 1 then every 4 weeks; alpelisib 300 mg per day. Response was assessed per RECIST v1.1 by blinded independent central review. The primary endpoint was PFS for the geda triplet vs. alpelisib/fulv. Secondary endpoints include PFS for the geda doublet vs. alpelisib/fulv, OS, safety, ORR, DOR, TTR, CBR, QOL, and geda PK. Statistical comparisons were performed by stratified log-rank test. Results: At data cut-off (3/09/2026; N=362), median follow-up for PFS was 11.0 mos. The trial met its primary endpoint. Median PFS for geda triplet (n=155) vs alpelisib/fulv (n=155) was 11.1 vs. 5.6 mos (HR, 0.50; 95% CI, 0.37-0.68; P&lt;0.0001). Median PFS for the geda doublet (n=52) vs alpelisib/fulv was 11.3 vs. 5.6 mos (HR, 0.51; 95% CI, 0.33-0.79; P&lt;0.0013). Safety was generally consistent with the individual agents, with low rates of D/C of assigned therapy due to tx-related adverse events (2.6% for geda triplet; 3.8% for geda doublet; 7.1% for alpelisib/fulv). All-grade tx-related hyperglycemia was 15.0%, 11.5%, 57.9% (grade 3: 2.6%, 0%, 13.8%), and all-grade tx-related stomatitis was 61.4%, 61.5%, and 34.2% (grade 3: 16.3%, 5.8%, and 5.3%), respectively, for geda triplet, geda doublet, and alpelisib/fulv. Conclusion: These data demonstrate that gedatolisib combination therapies offer a potential new standard of care as 2L treatment of HR+/HER2- ABC, irrespective of PIK3CA mutation status. Clinical trial information: NCT05501886 .

Individual locomotor bias drives counterclockwise motion in pedestrian crowds

One-Pot Electrochemical Synthesis of (Hydroxyamino)methanesulfonate from CO ₂ , Nitrate/Nitrite, and Sulfite

Framework for Speciation-Gated Mass Transfer at Liquid–Liquid Interfaces

Advancing the Korpelevich method: a new approach to equilibrium problems on Hadamard manifolds