Browse Articles

A phase III, randomized, open-label study of tunlametinib plus vemurafenib versus investigator's choice of therapy in patients with previously treated <i>BRAF</i> ^V600E -mutant metastatic colorectal cancer.

LBA3509 Background: The BRAF V600E mutation present in approximately 10% of metastatic colorectal cancer (mCRC) cases, confers a poor prognosis with limited response to chemotherapy. Tunlametinib is a novel, oral, high-potent MEK1/2 inhibitor. Synergistic effect of tunlametinib with vemurafenib was seen in BRAF mutant non-small cell lung cancer and mCRC in the previously published phase I trial (NCT03781219.). Based on promising Phase I/II data, we have this BRAF/MEK inhibitor dual-target regimen to advance to a Phase III randomized controlled trial in this population, addressing a significant unmet need. Methods: This randomized, open-label, phase III trial (NCT06008119) enrolled patients. with BRAF V600E–mutant mCRC after ≥1 prior line of systemic therapy. Patients were randomized 2:1 to tunlametinib (12 mg BID) + vemurafenib (720 mg BID) (T+V) or investigator's choice of therapy (control). A prespecified crossover from the control to the experimental arm is allowed upon IRC-confirmed disease progression. The primary endpoint is progression-free survival (PFS) assessed by a blinded Independent Review Committee per RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), and safety. The primary endpoint PFS analysis will use a stratified log-rank test, with the hazard ratio (HR) and its 95% confidence interval estimated using a Cox proportional hazards model. Results: As of the data cutoff date for this analysis (March 5, 2026), the full analysis set included 157 patients (105 T+V, 52 control). Based on investigator assessment (IRC assessment ongoing), median PFS was significantly prolonged with T+V versus control (4.2 months vs. 1.5 months; HR 0.374; 95% CI 0.252–0.555; P &lt; 0.001). The ORR was 37.1% (95% CI 27.9–47.1) in the T+V group versus 7.7% (95% CI 2.1–18.5) in the control group. P＜0.0001. DCR was 81.9% versus 38.5% (P &lt; 0.0001), respectively. OS data was immature. Treatment-related grade≥3 adverse events (TRAEs) occurred in 62.0% vs 44.2% of patients, Permanent treatment discontinuation due to TRAEs occurred in 0.9% and 3.8%, respectively. Safety was consistent with that known for each agent. Conclusions: This is the first phase III randomized controlled trial to demonstrate that a BRAF/MEK inhibitor combination (tunlametinib plus vemurafenib) significantly improves PFS and ORR compared with conventional chemotherapy-based regimens in previously treated BRAF V600E–mutant mCRC, with a manageable safety profile and the added benefit of a convenient all-oral regimen. Clinical trial information: NCT06008119 .

Scaling two-dimensional semiconductor nanoribbons for high-performance electronics

Single-Molecule Visualization of Nanoscale Spatiotemporal Dynamics of Charge-Carrier-Driven Photocatalysis on 2D InSe

Assessing paver screed compaction units and their impact on asphalt quality parameters through field trials

Abstract Ensuring the durability and longevity of asphalt pavements under traffic loads requires effective compaction during paving to resist deformation and withstand environmental stresses. While previous field-based studies have addressed asphalt compaction and selected screed settings, this study specifically links tamper speed and vibratory unit speed to pre-compaction, vertical void distribution, aggregate structure, and 3D surface roughness under real paving conditions. Two field trials using an ABG P6820D paver and BOMAG BW 174 roller were conducted with an AC 16 BN asphalt mix. Laboratory analyses evaluated layer thickness, bulk density, cavity structure, and surface roughness. The findings highlight that tamper speed significantly influences layer thickness and degree of compaction, while vibratory unit speed showed no substantial effect. Vertical void distribution was highly homogeneous (&gt; 98%) across pre-compacted areas, indicating tamper speed does not affect void distribution. Surface roughness tended to decrease with increased tamper speed, but vibratory unit speed showed no measurable benefit. No significant correlation was found between grain-to-grain distance or microstructural properties and vibratory unit speed. The study recommends minimizing adjustments to tamper speed during paving and suggests switching off the vibratory unit for the investigated AC 16 BN mixture under comparable paving conditions, provided that the required pre-compaction and surface quality are achieved. Regular monitoring of tamper wear and precise pre-paving adjustments are essential to enhance pavement quality and reduce maintenance costs.

Early results of COMPPARE, a prospective comparison of outcomes with proton and photon radiation in prostate cancer.

LBA5012 Background: There is a critical evidence gap on the relative benefits and harms of proton therapy (PT) compared with photon-based intensity-modulated radiation therapy (IMRT) in prostate cancer. Herein we report early results from COMPPARE, a non-randomized comparative study of outcomes with PT and IMRT in prostate cancer. Methods: Between 2018-2022, 2524 patients from 51 facilities (28 PT and 23 IMRT) enrolled in COMPPARE, including 1501 treated with PT and 1023 treated with IMRT, and were followed prospectively. Treatment naïve patients with localized prostate cancer except those with very high-risk disease were eligible. Treatment was pragmatic with daily standard fractionation (1.8-2.1 Gy) and moderate hypofractionation (2.4-3.1 Gy) permitted. Use of rectal spacers and androgen deprivation were at physician discretion. Patient-reported quality of life data and treatment team-reported toxicity and disease control outcomes were collected at baseline and pre-specified time intervals via VisionTreeOptimalCare; treatment planning and delivery data were collected via the Advanced Treatment Consortium. We analyzed 1404 PT patients and 939 IMRT patients. We report the early primary endpoint of the study, a comparison of patient reported bowel urgency and bowel frequency at 2-years using the EPIC tool, and the secondary endpoints of 2-year CTCAE v5 ≥ grade 2 gastrointestinal toxicity outcomes and 3-year freedom from biochemical progression (FFBP) results reported by the study teams. Results: Study sample size was targeted at 1,500 PT patients and 1,000 IMRT patients, and median follow-up time was 4.0 years. The primary endpoint and secondary toxicity 2-year endpoints focused on the alternative hypothesis of PT superiority. All results include inverse probability of treatment weighting. Using generalized linear mixed effects models, we found there to be no significant difference in EPIC bowel urgency scores (p = 0.324) or bowel frequency scores (p = 0.514) between PT and IMRT cohorts over time up to the 2-year endpoint. For grade 2 gastrointestinal toxicity, the 2-year cumulative incidence was 5.2% for PT and 5.6% for IMRT. Gray’s Test for competing risks showed a hazard ratio (HR) of 0.91 [95% confidence interval (CI): 0.65-1.28, p = 0.6] for PT versus IMRT. The exploratory non-inferiority endpoint of 3-year FFBP was 98.0% for PT and 97.9% for IMRT, and Gray’s Test showed a HR of 0.95 (95% CI: 0.52-1.71, p = 0.90). Conclusions: Analysis of early results of COMPPARE show no significant differences between PT and IMRT in patient reported bowel frequency and urgency, grade ≥2 gastrointestinal toxicity, or FFBP. Assessment of long-term disease control, late toxicity and secondary malignancy will require longer follow-up. Clinical trial information: NCT03561220 .

Effects of cooking with liquefied petroleum gas versus biomass on hemoglobin concentrations in pregnant women: a pre-specified exploratory analysis of the HAPIN trial

Abstract Evidence linking household air pollution exposure and blood hemoglobin concentration is lacking. We examine the effect of a liquefied petroleum gas cookstove and fuel intervention on hemoglobin concentration, along with associations between household air pollution exposures and hemoglobin concentration, among pregnant women. We enroll 800 pregnant women each in Guatemala, Peru, India, and Rwanda in an open-label randomized controlled trial (NCT02944682). In 3178 women (intervention=1585; control=1593), we measure hemoglobin concentration and 24-hour personal exposure to particulate matter with an aerodynamic diameter ≤2.5μm (PM 2.5 ), black carbon (BC), and carbon monoxide (CO) at three timepoints (9-20, 24-28, and 32-36 weeks gestation). We evaluate the effects of the intervention on hemoglobin concentration and conduct exposure-response analyses to examine associations between 24-hour personal exposure to measured pollutants and hemoglobin concentration. We identify a significant increase in hemoglobin in the intervention group (0.074 g/dL, 95% CI: 0.002, 0.145) compared to the control group. In exposure-response analyses, each 1ppm increase in CO exposure is associated with a 0.015 g/dL (95% CI: 0.008, 0.023) increase in hemoglobin. In our analyses, neither PM 2.5 nor BC are associated with hemoglobin concentration. Further research may be needed to examine the biological mechanisms underlying our findings.

Versatile Synthesis of Cyclopentenones via Skeletal Editing of Phenols

Near-infrared defect detection method for photovoltaic panels based on the FBCT-YOLOv8 algorithm

Efficacy and safety of asandeutertinib versus osimertinib as first-line treatment in EGFR-mutated NSCLC patients with brain metastases: Interim analysis of an open-label, multicenter, randomized, pivotal phase II study (ESAONA).

LBA2007 Background: Asandeutertinib (TY-9591), a novel EGFR-TKI candidate, demonstrated outstanding efficacy and manageable safety in its Phase I and Phase II studies. The ESAONA study was designed to compare the efficacy and safety between asandeutertinib and osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC) with brain metastases (BM). Methods: In the ESAONA study, treatment-naïve NSCLC pts with EGFR-sensitizing mutations and stable BM have been enrolled and randomized 1:1 to receive either asandeutertinib (160 mg orally, QD) or osimertinib (80 mg orally, QD). Randomization was stratified according to the number of intracranial lesions (&gt;3 or ≤3) and EGFR mutation type (L858R or 19Del). The primary endpoints were intracranial objective response rate (iORR) and intracranial progression-free survival (iPFS), assessed by the blinded independent central review (BICR) per RECIST version 1.1. Results: From August 14, 2023 to December 15, 2025, 224 eligible pts were enrolled and randomized to asandeutertinib (n=111) or osimertinib (n=113), with a median follow-up of 18.86 months (mo) and 19.12 mo, respectively. Baseline characteristics were well balanced. Results showed that asandeutertinib significantly improved the BICR-assessed iORR compared with osimertinib (95.5% [95%CI, 89.8%-98.5%] vs. 79.6% [95%CI, 71.0%-86.6%]; p=0.0004). INV-assessed iORR was 92.8% [95%CI, 86.3%–96.8%] in asandeutertinib and 77.9% [95%CI, 69.1%-85.1%] in osimertinib (p=0.0019). INV-assessed iORR per RANO-BM showed a consistent trend (91.9%, [95%CI, 85.2%-96.2%] vs. 77.9%, [95%CI, 69.1%-85.1%], p=0.0039). BICR-assessed Median iPFS (miPFS) was not reached [95%CI, 22.24–NA] in asandeutertinib and 17.51 mo [95%CI, 15.18–NA] in osimertinib (HR 0.46 [95%CI, 0.28-0.76]; p=0.0020). The trend in miPFS was consistent across subgroups. INV-assessed miPFS was not reached [95%CI, 21.45–NA] in asandeutertinib and 17.51 mo [95%CI, 15.38–21.36] in osimertinib (HR 0.56 [95%CI, 0.36-0.89]; p=0.0122). INV-assessed miPFS per RANO-BM also favored asandeutertinib (22.64 vs. 17.51 mo; HR 0.60 [95%CI, 0.39-0.94]; p=0.0232). BICR-assessed mPFS was not reached [95%CI, 17.22–NA] with asandeutertinib vs 17.22 mo [95%CI, 15.18–19.55] with osimertinib (HR 0.64 [95%CI, 0.41-1.00]; p=0.0473). Systemic efficacy was numerically favored asandeutertinib, and OS remained immature. Treatment-related adverse events (TRAEs) was 99.1% in asandeutertinib and 95.6% in osimertinib. Treatment-related serious adverse events was 10.8% in asandeutertinib and 7.1% in osimertinib. Conclusions: Asandeutertinib significantly improved iORR and iPFS compared to osimertinib, with manageable safety profile, supporting its potential as a new first-line treatment for EGFR-mutated NSCLC pts with BM. Clinical trial information: NCT05948813 .

The distinct trimeric structure of the immunodominant chlamydial antigen Major Outer Membrane Protein

Optimized Biomimetic Syntheses of Discorhabdin B and Aleutianamine Drives a Deeper Exploration of Their Anticancer Potential

Incremental model predictive control of PMSM based on parameter tuning of multi-layer perceptron neural network and disturbance observer

Adjuvant sintilimab-capecitabine versus capecitabine alone in locoregionally advanced nasopharyngeal carcinoma with suboptimal response to induction chemotherapy: An open-label, randomized, controlled, phase 2 trial.

LBA6005 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the current standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC); however, patients with a suboptimal response to IC remain at high risk of disease progression. Although adjuvant capecitabine has demonstrated efficacy in high-risk LA-NPC, whether intensifying adjuvant therapy by adding sintilimab, a highly selective, fully humanized monoclonal PD-1 inhibitor to capecitabine, can further improve survival outcomes remains unclear. Methods: This open-label, randomized, phase 2 trial enrolled patients aged 18–70 years with untreated, non-keratinising, stage II–IVA LA-NPC according to the eighth edition of the American Joint Committee on Cancer classification system with suboptimal response to IC, defined as detectable EBV DNA and/or stable or progressive disease after platinum-based IC. After CCRT, all patients were randomly assigned (1:1) to receive either adjuvant sintilimab plus capecitabine or capecitabine alone. Sintilimab (200 mg intravenously) was administered on days 1 and 14 after randomization as a lead-in phase, and then every 3 weeks starting 28 days after CCRT, combined with capecitabine (1000 mg/m² twice daily, days 1–14) for eight cycles; the control group received capecitabine alone on the same schedule starting 28 days after CCRT for eight cycles. The primary endpoint was 2-year progression-free survival (PFS) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the assigned treatment. The study was registered at ClinicalTrials.gov (NCT05201859), and patients are under follow-up. Results: One hundred fifty patients were randomised (76 to sintilimab–capecitabine group; 74 to capecitabine group). At a median follow-up of 41 (IQR 35-44) months, the 2-year PFS was 88.2 % in the sintilimab–capecitabine group and 87.8% in the capecitabine group (stratified HR 0.85; 90% CI 0.43–1.70; p=0.77). Grade 3-4 adverse events were reported in 25 (34%) patients in the sintilimab–capecitabine group and in 22 (31%) patients in the capecitabine group; hand-foot syndrome was the most common adverse event in both groups (8% vs. 10%). Immune-related grade 3 myocarditis were occurred in 2 (3%) patients in the sintilimab–capecitabine group. No treatment-related deaths occurred. Conclusion: In patients with LA-NPC who had a suboptimal response to IC, intensification of adjuvant therapy with the addition of sintilimab to capecitabine did not result in a significant improvement in progression-free survival. Future studies are warranted to focus on biomarker-driven patient selection and optimization of immunotherapy sequencing with conventional treatments. Clinical trial information: NCT05201859 .

Photoinduced H-Bonding EDA complex-enabled skeletal editing of furans to pyridazines

Emissive Colloidal GaAs Quantum Dots

Enhancing the detection of LTP through lyophilized protein samples and NIR spectroscopy with explainable deep learning

A multicenter randomized phase II trial of AHCC combined with multidisciplinary treatment for resectable/borderline resectable pancreatic ductal adenocarcinoma (jRCTs051200029).

LBA4226 Background: Malnutrition, impaired immunity, and limited tolerance to intensive chemotherapy remain major challenges in the multidisciplinary treatment of pancreatic ductal adenocarcinoma (PDAC). AHCC, a standardized extract derived from cultured Lentinula edodes mycelia, has demonstrated immunomodulatory, anti-inflammatory, and antioxidant effects and may enhance tolerance to chemotherapy. This multicenter randomized phase II trial was designed to evaluate whether long-term administration of AHCC improves clinical outcomes in patients with resectable (R) or borderline resectable (BR) PDAC undergoing multimodal treatment. Methods: This investigator-initiated, double-blind, placebo-controlled, multicenter phase II trial enrolled 230 patients with histologically confirmed resectable or borderline resectable PDAC across eight high-volume centers in Japan. Patients were randomly assigned in a 1:1 ratio to receive oral AHCC (3.0 g/day) or matched placebo, starting from the initiation of neoadjuvant therapy and continuing for up to two years postoperatively. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included 2-year overall survival (OS), treatment compliance, chemotherapy-related adverse events, and longitudinal changes in nutritional and immune parameters across treatment phases, including neoadjuvant therapy, adjuvant therapy, and post-recurrence treatment. Survival analyses will be conducted according to the intention-to-treat principle. Results: A total of 230 patients (115 per arm) were analyzed with balanced baseline characteristics. The resection rate tended to be higher in the AHCC group than in the placebo group (86.1% vs 77.4%, P=0.088). For the entire cohort, median OS was 45.1 months and median DFS 22.6 months. The primary endpoint, 2-year DFS, did not differ between groups (22.6 vs 19.2 months, P=0.809). However, median OS was significantly longer in the AHCC group (NR) than in the placebo group (38.8 months, P=0.026). Among patients with recurrence (n=135), post-recurrence survival was significantly longer in the AHCC arm (20.8 vs 10.8 months, P=0.006), whereas no difference was observed among patients without recurrence (both NR, P=0.720). Completion of neoadjuvant and adjuvant therapy rates were similar between groups. At 24 months after treatment initiation, immune-nutritional indices were significantly better preserved in the AHCC group, including NLR, PNI, CAR, and PLR (all P&lt;0.001). Conclusions: Although AHCC did not significantly improve DFS, it was associated with significantly prolonged overall survival, particularly among patients with recurrence. Preservation of immune-nutritional status may have contributed to the observed survival benefit. Clinical trial information: jRCTs051200029.

Decoupling electron transfer defines a quantitative kinetic framework for oxygen evolution catalysis

Abstract The oxygen evolution reaction underpins many energy conversion technologies, yet its performance is fundamentally constrained by sluggish reaction kinetics at catalyst surfaces. Current catalyst design remains largely empirical because most strategies correlate bulk structural descriptors with overall activity rather than resolving the intrinsic kinetics of elementary reaction steps. Here, we show that open-circuit voltage–pulse voltammetry can quantitatively determine the * OOH formation rate, a rate-determining step in oxygen evolution. Unlike conventional electrochemical techniques, this method isolates * OOH formation-related electron transfer by interrupting electron transfer from electrocatalyst to external circuit while sustaining electron supply from hydroxide ions. Coupling this descriptor with a pulse voltammetry method for quantifying * OH deprotonation kinetics yields a unified, step-resolved kinetic framework that reveals how different dopants selectively accelerate either * OOH formation or * OH deprotonation. Fe primarily facilitates * OOH formation, whereas Mn selectively promotes * OH deprotonation. Guided by these insights, a rationally designed NiFeMn catalyst concurrently enhances both processes, delivering improved oxygen evolution performance. This methodology provides a practical means to quantify elementary reaction kinetics and accelerate the discovery of high-performance electrocatalysts.

Electronic-Structure Modulation in NiRu Alloys To Alleviate Hydrogen Poisoning for Robust Photothermal Ammonia Decomposition

Trace element mobility during the injection of water-dissolved CO2 into basalts

Abstract In-situ carbon mineralization in basalts has been identified as a permanent and scalable method to sequester CO 2 in the subsurface. The extent of potentially toxic trace element mobilization during basalt dissolution, however, remains poorly constrained. The Jizan carbon sequestration pilot was undertaken to assess the potential for carbon disposal through the mineralization of water-dissolved CO 2 injected into subsurface basalts in arid regions. The temporal evolution of trace element and potentially toxic metal concentrations in the Jizan groundwater during and following the injection of CO 2 -charged water and its recirculation has been assessed. Twenty-eight representative production well fluid samples were selected and analyzed by ICP-MS. Element mobility was quantified by comparing the increase in concentration of the selected elements in the aqueous phase to the corresponding increase in sodium concentration. Results indicate that the mobility of trace elements in the Jizan system is limited, with the average mobility of most trace elements remaining below 20% of that of sodium. Furthermore, the maximum measured concentrations of most trace elements are significantly below the acceptable levels in drinking water before, during, and after the CO 2 injection. These observations suggest the risk of groundwater pollution during in-situ carbon mineralization efforts in basalt is likely minimal.