Browse Articles

Detection and countermeasure integrated framework against false data injection attacks in multi-area coupled power systems

Overcoming Size-Dependent Magnetic Thermal Stability via Atomical Coherence

Genome-wide identification, characterization and expression analysis of the subtilisin-like protease gene family in Quercus ilex in response to Phytophthora cinnamomi

Adjuvant hepatic arterial infusion pump chemotherapy with floxuridine for patients with resectable colorectal liver metastases and a low clinical risk score: A randomized controlled trial—The PUMP trial.

LBA3506 Background: Recurrence after local treatment for colorectal liver metastases (CLM) occurs in up to 70% of patients, frequently confined to the liver. Dutch guidelines do not recommend adjuvant chemotherapy, because three randomized controlled trials (RCTs) have shown no overall survival (OS) benefit of perioperative systemic chemotherapy in resectable CLM. Hepatic arterial infusion pump (HAIP) chemotherapy delivers high doses of floxuridine directly to the liver. This trial evaluated the effectiveness of adjuvant HAIP chemotherapy with floxuridine compared to resection alone in patients with resectable CLM and a low clinical risk score (CRS). Methods: This is an open-label, investigator-initiated, multicenter, randomized phase III trial. Adult patients with resectable CLM, no extrahepatic disease, and CRS 0–2 were randomized 1:1 to resection plus adjuvant HAIP chemotherapy with floxuridine versus resection alone, both without adjuvant systemic chemotherapy. Preoperative systemic chemotherapy prior to randomization was allowed. Patients in both groups who signed informed consent but did not fulfill inclusion criteria at the time of surgery were excluded and replaced. Patients were scheduled for 6 cycles of HAIP chemotherapy with floxuridine (0.12 mg/kg/day) that was initiated 4–12 weeks after placement of a Tricumed constant flow pump. The primary endpoint was progression-free survival (PFS) calculated from the date of surgery to the date of a recurrence or death. Secondary endpoints included hepatic PFS (hPFS) and ninety-day mortality. Survival was estimated using Kaplan-Meier method and compared using a log-rank test. Results: Between August 2018 and March 2026, 243 patients were randomized to resection followed by adjuvant HAIP (n=120) or resection alone (n=123). At time of surgery, 25 patients were excluded due to presence of extrahepatic disease, unresectable CLM or histopathological confirmation of benign disease. In this analyses, 110 patients were included in the resection and adjuvant HAIP group and 108 patients in the resection alone group. In the HAIP group, 100 patients (91%) initiated HAIP chemotherapy, and the median number of administered cycles was 5 [IQR 3-6]. Treatment was discontinued in 8 patients (8%) due to recurrence and in 32 patients (32%) due to toxicity. The median PFS was 15.0 months in HAIP group vs 16.0 months in resection alone group (HR 0.88; 95% CI 0.62–1.25; p=0.48). The median hPFS was 37.6 months in HAIP group vs 21.8 months in resection alone group (HR 0.80; 95% CI 0.54–1.17; p=0.25). Ninety-day postoperative mortality was observed in 4 patients (3.3%) in the HAIP group and in 1 patient (0.8%) after resection alone. No mortality was attributed to pump placement or HAIP chemotherapy. Conclusion: In patients with resectable CLM and a low CRS, no improvement in PFS after adjuvant HAIP chemotherapy with floxuridine compared to resection alone could be demonstrated. Mature results for overall survival are expected in 2029. EudraCT number: 2018-001696-21. Clinical trial information: 2018-001696-21.

Prefrontal parvalbumin neurons mediate working memory in a task demand-dependent manner

Non-innocent Spectators: Decoupling the Role of Cations and Anions in Modulating Nanoparticle Synthesis

Perturbation-evoked cortical responses and altered causal information flow reflect more effortful but less efficient postural control in patients after ACLR

Abstract Effective responses to sudden mechanical perturbations require coordinated neural processes for generating rapid, situation-specific postural reactions. Sensorimotor impairments following anterior cruciate ligament reconstruction (ACLR) may disrupt this coordination and contribute to inefficient postural control strategies. Therefore, the present study investigated perturbation-evoked behavioral and cortical dynamics in individuals after ACLR compared with asymptomatic controls. Seventeen athletes after ACLR (8 female, 23.6 ± 3.7 years) and thirteen controls (4 female, 25.9 ± 4.2 years) underwent 100 unpredictable platform translations in bipedal stance. Postural responses were examined using statistical parametric mapping of anterior–posterior hip acceleration. Cortical dynamics were assessed via mobile electroencephalography by quantifying perturbation-evoked potentials (PEP N1) and effective connectivity derived from renormalized partial directed coherence. Compared to controls, the ACLR group exhibited significantly higher hip acceleration during early voluntary adjustment and late re-stabilization phases of the postural response. Due to the different approaches of group-level comparisons, 20 participants (11 ACLR / 9 CON) showing characteristic event-related potentials were used for the PEP analysis, whereas 30 participants (17 ACLR / 13 CON) were eligible for the effective connectivity analysis utilizing probabilistic dipole densities. N1 amplitudes of the PEPs were significantly higher in the ACLR group, whereas fronto-central information flow was significantly lower early after perturbation, but significantly higher during re-stabilization. These results suggest that postural responses after ACLR may rely on increased cortical activation and altered dynamics within a fronto-central network,  pointing at greater voluntary control and reduced automatization of sensorimotor processes, likely predisposing individuals after ACLR to an elevated risk of dysfunction and re-injury.

frontMIND: Phase 3 study of tafasitamab (Tafa) plus lenalidomide (Len) and R-CHOP for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

LBA7000 Background: ~40% of DLBCL pts are not cured with first-line (1L) R-CHOP, underscoring a significant unmet need for more effective 1L regimens. Tafa (anti-CD19 mAb) + Len-R-CHOP in the phase 1b First-MIND study demonstrated safety and efficacy in pts with newly diagnosed disease. frontMIND, a phase 3, double-blind, placebo-controlled study, compared Tafa-Len-R-CHOP vs R-CHOP in pts with high-risk aggressive BCLs. Methods: Pts aged 18–80 y with newly diagnosed, high-intermediate/high-risk DLBCL or HGBL (IPI 3–5, aaIPI 2–3 if ≤60 y) and ECOG PS 0–2 were randomized 1:1 to Tafa-Len-R-CHOP or R-CHOP. Primary endpoint was investigator-assessed PFS; secondary endpoints included: EFS, OS, CR, ORR, safety. Results: At primary analysis (data cutoff Oct 20, 2025), 899 pts were randomized to Tafa-Len-R-CHOP (n=448) or R-CHOP (n=451); baseline characteristics were similar between arms. With a median follow-up of 35.2 mo, Tafa-Len-R-CHOP achieved a statistically significant improvement in PFS vs R-CHOP (HR 0.75 [95% CI: 0.59, 0.96]; P =0.019) in the overall population; in pts with centrally confirmed lymphoma subtypes (n=773), PFS HR was 0.68 (95% CI: 0.52, 0.88) and 24-mo PFS was 72.7% vs 62.2%. PFS benefit was observed with Tafa-Len-R-CHOP in both molecular COO subtypes, ABC and GCB (data will be presented). Tafa-Len-R-CHOP significantly improved EFS vs R-CHOP; CR and ORR were similar between arms and HR for OS was 0.85 (final OS planned at 5y) (Table). Any-grade TEAEs were similar in treatment arms (98.6% vs 97.1%); more grade ≥3 TEAEs occurred with Tafa-Len-R-CHOP vs R-CHOP (86.7% vs 76.1%). Discontinuations due to TEAEs occurred in 25.7% vs 17.9% and deaths due to TEAEs in 5.9% vs 3.8% of pts for Tafa-Len-R-CHOP vs R-CHOP. Overall, there were fewer deaths with Tafa-Len-R-CHOP vs R-CHOP (18.5% vs 21.7%). Conclusions: The primary endpoint of frontMIND was met; Tafa-Len-R-CHOP resulted in a significant 25% reduction in risk of disease progression or death compared with R-CHOP, with an 8.2% difference in 24-month PFS rate in the overall population and 10.5% difference in pts with centrally confirmed lymphoma subtypes. TEAEs were manageable and consistent with the expected safety profile. Tafa-Len-R-CHOP represents a potential new 1L standard of care for pts with both COO subtypes of high-risk DLBCL or HGBL. Clinical trial information: NCT04824092 . Efficacy outcomes by treatment arm.* Variable Tafa-Len-R-CHOP(n=448) R-CHOP(n=451) HR or OR(95% CI) P value PFS, # events (%) † 121 (27.0) 155 (34.4) 0.75 (0.59, 0.96) 0.019 PFS rate at 24 mo, % 71.1 62.9 − − PFS rate at 36 mo, % 67.3 60.7 − − EFS, # events (%) 154 (34.4) 191 (42.4) 0.79 (0.64, 0.97) 0.026 OS, # events (%) 82 (18.3) 95 (21.1) 0.85 (0.63, 1.14) 0.270 CR at EOT, n (%) 292 (65.2) 294 (65.2) 0.998 (0.76, 1.31) 0.987 ‡ ORR at EOT, n (%) 360 (80.4) 343 (76.1) 1.290 (0.94, 1.78) 0.120 ‡ *Investigator-assessed. † Progressive disease or death from any cause. ‡ Nominal P value.

Minimizing galvanic corrosion for durable anode-less aqueous zinc batteries

Ligand-Enabled Ag-Free Cross-Coupling of Methylene C(sp ³ )–H Bonds in Aliphatic Acids with C(sp ² ) Bromides

A survey of respiratory physicians on investigating and managing tuberculous pleuritis

Abstract Diagnosing tuberculous pleuritis (TBP) is challenging. No consensus currently guides its workup and management in tuberculosis (TB)-endemic regions. An online survey was conducted to assess real-world practices of respiratory physicians when approaching new-onset unilateral pleural effusion and the likelihood of TBP being considered in the diagnostic workup. Responses from 414 respiratory physicians across 15 countries/regions were analyzed, with 98.8% from intermediate-to-high TB burden areas. TBP was frequently considered as a differential diagnosis for new-onset unilateral pleural effusion by 80.4% of respondents. Heterogeneity was observed in the diagnostic and therapeutic approaches among respondents. Initial investigations, including pleural fluid Mycobacterium tuberculosis (MTB) culture, adenosine deaminase and pleural biopsy for histology, were performed variably. Selection of TBP-specific diagnostic tests was correlated with regional TB burden and initial consideration of TBP. Varied perceptions of diagnostic test accuracy were also evident among respondents. A definitive TBP diagnosis, supported by histological or microbiological proof, was required by 60.9% of respondents before anti-TB treatment was initiated. 77.8% of respondents had experienced a revision of the diagnosis of probable TBP cases following empirical anti-TB treatment failure. These findings highlight the need to strengthen the diagnosis and management of TBP in surveyed regions.

HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer

PURPOSE The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582 ) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (MBC). METHODS Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety. RESULTS Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor–positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs. CONCLUSION Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

Hybrid auxetic metamaterial platforms enabling multiscale isotropic expansion for distortion-free stretchable displays

Interfacial Oxide Engineering of TiN Antenna-Reactor for Durable Photothermal Dry Reforming of Methane

Joint capsule pathology as a contributor to pain in hallux valgus: a histological study

Bridging the Gap: Advancing First-Line Therapy for Patients With Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Ordered nanoplastic-elastomer networks resolve conflict between softness and stability

Arab gum coating enhances the bioavailability and therapeutic potential of nanoselenium in cisplatin-induced testicular toxicity

Abstract While Cisplatin remains a cornerstone of oncological intervention, its induction of systemic oxidative stress arranges a deleterious cascade that compromises male reproductive homeostasis. Selenium nanoparticles (SeNPs) may protect against oxidative stress and capping them with Arab gum (AG) could enhance their therapeutic efficacy. This study investigated the comparative gonadoprotective potential of Selenium Nanoparticles (SeNPs) and Arab gum (AG)-coated SeNPs (AG-SeNPs) against Cis-induced testicular dysfunction. Forty-five male Wistar rats were randomized into nine experimental groups: four baseline controls (Normal, AG, SeNPs, and AG- SeNPs) and five treatment groups receiving AG, SeNPs, AG-SeNPs, or a physical mixture of AG + SeNPs following Cis administration. Assessment parameters included the gonadosomatic index, biochemical markers of oxidative stress (CAT, GPX, MDA), and pro-inflammatory cytokines (TGF-beta, TNF-α and IL-6). Testicular integrity was further evaluated via histopathology, PCNA protein expression (cellular proliferation), and DNA fragmentation analysis using the Comet assay and apoptotic markers (Caspase-3 and Cytochrome C release). Administration of AG-SeNPs demonstrated superior gonadoprotective efficacy compared to uncoated SeNPs or physical mixtures. AG-SeNPs significantly restored redox homeostasis, via augmenting antioxidant enzyme activities (CAT, GPX) and reducing lipid peroxidation (MDA). Furthermore, AG-SeNPs significantly downregulated inflammatory signaling (TGF-beta, TNF-α and IL-6) and mitigated DNA damage. The treatment preserved genomic stability and inhibited the intrinsic apoptotic pathway by suppressing Cytochrome C release and Caspase-3 activation. Histological examination confirmed the restoration of seminiferous tubular architecture and enhanced cellular proliferation (PCNA expression). These findings suggest that AG-coating enhances the therapeutic index of SeNPs, likely due to improved bioavailability and synergistic antioxidant properties. AG-SeNPs represent a promising nanomedicine-based strategy for mitigating the gonadotoxic side effects of cisplatin-based chemotherapy.

Role of neoadjuvant versus adjuvant chemotherapy, dose density, and treatment schedule in biologically high-risk HR+/HER2- breast cancer: A pooled analysis of the WSG ADAPT-HR+/HER2- and PlanB trials.

LBA515 Background: Dose-dense anthracycline-taxane chemotherapy (CTx) is standard for high-risk early breast cancer (eBC) and is often given in the neoadjuvant setting if CTx is clearly indicated (e.g., recurrence score, RS > 25 and/or > 4 positive lymph nodes by imaging) or if downstaging is needed. While dose-dense CTx improves outcomes irrespective of hormone receptor (HR) status in meta-analyses, its benefit in node-negative HR+ eBC appears limited. Further meta-analyses on neoadjuvant vs adjuvant use, and on mono- vs combined therapy, showed mixed results. These findings highlight an unmet need for a refined treatment selection, informed by the assessment of relative survival benefit. We therefore pooled the WSG ADAPT-HR+/HER2- and PlanB trials to estimate the impact of dose density, anthracycline use, and treatment setting on survival. Methods: Invasive (iDFS), distant disease-free survival (dDFS), and overall survival (OS) were analyzed retrospectively in a pooled analysis of HR+/HER2- patients (pts) in ADAPT-HR+/HER2- (n = 2331) and PlanB (n = 2220) who received chemotherapy and had follow-up data (data cut: Jan 26, 2026). In ADAPT-HR+/HER2-, pts at high-risk received 8× weekly nab-paclitaxel vs. 4× biweekly sb-paclitaxel, followed by epirubicin + cyclophosphamide (EC) in either the neoadjuvant or adjuvant setting. PlanB randomized pts at intermediate- to high-risk to adjuvant 4× EC followed by 4× docetaxel (EC-T) vs. 6× TC. To minimize bias, predefined uniform cross-trial subgroups (RS > 25 any pN; pN2–3 any RS) were considered here, and propensity scoring for non-random allocations (neoadjuvant vs adjuvant CTx in ADAPT-HR+/HER2-, physician choice). Results: This pooled analysis included 1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2-3 eBC. Dose-dense anthracycline or paclitaxel yielded inferior iDFS and dDFS than q3w docetaxel, even after adjustment for cT, age, and grade. This effect, favoring a (longer) docetaxel-based CTx, was present among N2-3 pts with RS ≤25, who showed better iDFS, dDFS, and OS, and among RS > 25 pts (in particular, in N0-1), who showed better dDFS. Informed by these results, we assessed the impact of anthracyclines in PlanB pts with RS > 25 and/or N2-3 and observed no significant survival differences. There was no significant survival difference between neoadjuvant vs adjuvant CTx in the corresponding subset of ADAPT-HR+/HER2- pts, even in propensity-scored analysis. Conclusions: Our exploratory retrospective analysis does not show a significant survival difference by anthracycline use or treatment setting (neoadjuvant vs adjuvant) in high-risk HR+/HER2- eBC pts who are candidates for CTx. Optimal use of dose-dense CTx in the context of docetaxel-based treatment requires further investigation. Clinical trial information: NCT01779206 ; NCT01049425 .

Cryoelastic and cryochromic organic crystals