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Solvent-Modulated Orthogonal Release from Covalent Organic Frameworks Enables Sequential Multiomics Enrichment

Genetic influences on accelerometer-measured physical activity and sedentary time in children: sex-specific patterns from a Swedish twin study

Abstract Physical activity (PA) plays a key role in children’s health, yet it remains unclear why girls are often less active and more sedentary than boys. This study examined genetic and environmental (shared and non-shared) influences on device-measured PA and sedentary time (SED) across girls and boys. This cross-sectional study contained data on zygosity, sex, PA, and SED for 2046 9-year-old twins in Sweden. The accelerometer-measured PA was expressed as the proportion of time in SED, light (LPA), moderate (MPA) or vigorous PA (VPA). Structural equation modelling within a twin framework estimated the heritability of PA and SED, decomposing variance into additive genetic (A), shared environment (C), and non-shared environment (E). Quantitative sex differences were examined by allowing the variance components (A, C, E) to differ across sexes. In the total cohort, genetic contribution was highest in VPA (A total : 0.64) but lower in SED, LPA and MPA (A total : 0.50–0.55). Boys and girls had differing patterns of genetic contributions, with the largest contributions among girls found for LPA (A girl : 0.44; A boy : 0.37) while the genetic contribution in VPA was larger in boys (A girl : 0.15; A boy : 0.57), and the difference was statistically significant for VPA (p = 0.001). While the non-shared environment was similar in all models, the shared environment showed the opposite pattern to the genetic contributions. This twin study shows that genetic influences on PA and SED differ by sex, highlighting the importance of considering how biological mechanisms that drive activity patterns might differ across sex, especially in vigorous physical activity.

Preliminary injection site reaction immune response results from open-label arm of ongoing phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in patients with breast cancer with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy (Flamingo-01).

LBA538 Background: This phase III trial is a prospective, randomized, double-blinded, multi-center study (NCT05232916) in HLA-A*02 patients at approximately 140 sites in the US and Europe. A third non-randomized arm of approximately 250 non-HLA-A*02 patients is now fully enrolled and preliminary immune response data is presented below. GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. Methods: After standard of care neoadjuvant and adjuvant therapy, 6 intradermal injections of GLSI-100 will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up. Immune responses to GP2 were measured over time using delayed-type-hypersensitivity (DTH) skin tests and injection site reactions (ISRs). The patient population is defined by these key eligibility criteria: 1) HER2/neu positive and HLA, 2) Residual disease or High risk pCR (Stage III at presentation) post neo-adjuvant therapy, 3) Exclude Stage IV, and 4) Completed at least 90% of planned adjuvant trastuzumab-based therapy. Results: All patients (n=247) were vaccinated with GLSI-100. Injection site reactions and erythema (redness) were assessed at various time points and represent an in vivo immune response in patients. The ISR orthogonal mean was measured 48-72 hours following vaccination with GLSI-100. For GP2 treated patients, there was a significant increase in the percentage of patients experiencing ISRs in the 4th, 5th or 6th vaccination compared to the ISRs from the 1st vaccination. In this preliminary analysis, the frequency of ISRs increased significantly from 20.2% of the patients experiencing an ISR after the first vaccination to 55.3% of the patients experiencing an ISR after the 4th, 5th or 6th vaccination (McNemar p < 0.001). The study is ongoing and data collection and cleaning continue, so final results may vary. Conclusions: Preliminary injection site reaction data comparing vaccination over time in GLSI-100 treated non-HLA-A*02 patients showed a significant increase in immune response. Future studies may explore the use of immune responses to assess correlation of DTH to ISRs, immunogenicity of GLSI-100 by specific HLA type, timing of boosters to sustain immunity, clinical site performance, and the discontinuation of treatment for non-responders. Funding: This trial is supported by Greenwich LifeSciences. Clinical trial information: NCT05232916 .

Diffusional Priority Enables Kinetic ⁶ Li Selectivity in a Covalent Organic Framework

Occupational hazard awareness and safety-related knowledge among EMS students: evidence of a potential gap

Ethical Design and Implementation of Monetary Transfer Interventions in Clinical Cancer Research

Metal–Organic Framework Goes Perovskite: A Self-Healing Neutral X-Site Perovskite Ferroelastic Crystal

Long-Range White-Matter Pathways Enable Efficient Spontaneous Neural Activity Propagation in the Human Brain

Efficient brain-wide communication requires neural activity to traverse long anatomical distances rapidly. Here we examine how propagation timing is jointly associated with spatial geometry, functional network organization, and long-range white-matter pathways and their microstructural properties. And we ask whether the same rules govern epileptiform and physiological activity. Using stereo-EEG and diffusion spectrum imaging from 47 epilepsy patients (26 males and 21 females), we quantified interregional propagation with two complementary delay estimators: event-based interictal epileptiform discharge (IED) traveling waves and continuous lagged-correlation delays during IED-free periods. We found that IED propagation traversing gray and white matter formed reproducible spatiotemporal motifs that deviated from randomized null models, indicating structured routing rather than random spread. Epileptiform and physiological propagation delays increased over short ranges but saturated at longer distances, indicating that geometry alone cannot account for long-range fast propagation. Beyond geometry, stronger structural connectivity and higher functional connectivity were associated with shorter delays, and intrinsic functional modules facilitated efficient communication: within-network propagation was faster than between-network propagation. Crucially, diffusion-derived quantitative anisotropy (QA) revealed a microstructural mechanism for long-range fast propagation: long-range white-matter tracts showed higher QA, and QA was positively associated with apparent propagation velocity. Together, these results identify convergent, architecture-dependent constraints on propagation timing that generalize across epileptiform and normal activity, providing a principled bridge between macroscale connectome organization and fast intracranial spatiotemporal dynamics.

Reproductive toxicity of a nano-insecticide (chlorpyrifos) on male albino mice

Abstract Chlorpyrifos (CPF) is a commonly used organophosphorus insecticide in agriculture, and it is linked to reproductive toxicity in males by disrupting the endocrine system. Most previous studies focus on its traditional form, neglecting its nanoform, which may pose a greater risk due to enhanced bioavailability. Our study evaluated the reproductive toxicity of a nano-emulsion of CPF (CPF-NE) in male albino mice. Mice were divided into four groups ( n  = 10 per group): a control and three treated groups receiving CPF-NE via oral gavage at doses of 3.79, 7.58, and 15.16 mg/kg body weight daily for 35 days. We assessed gonadosomatic index (GSI), reproductive performance (mating success and fertility rate), sperm parameters, DNA fragmentation, hormonal levels (testosterone, FSH, LH), total antioxidant capacity (TAC), malondialdehyde (MDA), and catalase (CAT). Post-treatment testes were examined histologically. Results showed that CPF-NE significantly decreased GSI (from 0.66 ± 0.02 in controls to 0.31 ± 0.02 in high-dose, p  < 0.001), reproductive performance (fertility index dropped to zero at high dose), sperm viability (from 74 ± 1.6% to 43.1 ± 1.7%, p  < 0.001), and testosterone (from 4.2 ± 0.3 ng/mL to 1.8 ± 0.2 ng/mL, p  < 0.001), while increasing FSH, LH, MDA, and DNA fragmentation. Histopathological findings indicated reduced tubular diameters, decreased epithelial heights, and disrupted testicular structure. In conclusion, CPF-NE adversely affects male fertility by increasing oxidative stress and DNA damage.

Gabapentin plus tramadol versus tramadol alone for chemoradiotherapy-induced oral mucositis pain in head and neck cancer: Results of a randomized phase III trial.

LBA12001 Background: Oral mucositis-related pain during concurrent chemoradiation (CTRT) for head and neck squamous cell carcinoma (HNSCC) significantly impairs quality of life (QoL) and frequently necessitates opioid escalation. Despite tramadol-based analgesia, up to one-third of patients require stronger opioids. Gabapentin may improve pain control by targeting the neuropathic component of mucositis-related pain. We conducted a randomized phase III trial evaluating whether the addition of gabapentin to tramadol improves mucositis pain control during CTRT. Methods: In this single-center, open-label, randomized phase III superiority trial, 154 patients with HNSCC receiving radical or adjuvant CTRT who developed CTCAE v5.0 grade ≥1 mucositis with pain [Visual Analogue Scale (VAS) ≥1] were enrolled. Eligible patients were aged 18–70 years with ECOG performance status 0–2. Patients were randomized 1:1 to tramadol plus topical anaesthetic (Arm A) or gabapentin plus tramadol and topical anaesthetic (Arm B). Gabapentin was escalated from 300 mg/day to a maximum of 1,800 mg/day. The primary endpoint was pain control measured as the area under the curve (AUC) of VAS pain scores following the first dose of analgesic. Secondary endpoints included analgesic escalation at day 7, weight loss at the end of CTRT, QoL, treatment compliance, adverse events, and treatment delays. With 154 patients, the study had 80% power to detect an effect size of 0.5 at a two-sided α of 0.05. The study was registered with the Clinical Trials Registry-India (CTRI/2020/03/024269). Results: A total of 154 patients were randomized. Median age was 49 years (IQR 42–57), and most patients had locally advanced disease (T3–4 77.3%, N2–3 69.5%, stage IVA–B 83.1%). The primary endpoint, pain control measured by AUC of VAS scores following the first dose of analgesic, was similar between the two arms [median AUC 1170 (95% CI 727–1638) vs 1080 (95% CI 802–1800)]. However, analgesic escalation requiring morphine occurred significantly more frequently in the tramadol arm compared with the gabapentin arm (37.3% vs 12.0%, p < 0.001), corresponding to an absolute risk reduction of 25.3%. Grade ≥2 weight loss occurred in 33.8% vs 27.3% of patients (p = 0.382), and radiotherapy interruptions occurred in 6.5% vs 1.3% (p = 0.096), favoring the gabapentin arm. QoL scores were comparable between arms. Gabapentin-related toxicities were mostly grade 1–2 and manageable. Conclusion: Addition of gabapentin to tramadol during CTRT significantly reduced the need for opioid escalation for mucositis-related pain in patients with head and neck cancer. Although early pain scores were similar, gabapentin demonstrated a clinically meaningful opioid-sparing effect, suggesting it may be an effective strategy for managing CTRT-induced mucositis pain. Clinical trial information: CTRI/2020/03/024269.

Harnessing Strong Chiroptical Nonlinearity in Carbene-Copper-Amides through Center-Specific Chirality: An Approach to Amplified Dissymmetry

Positive Bias in Value-Based Decision Making: Neurocognitive Associations with Resilience

Biased information processing plays an important role in mental disorders. This study investigates choice biases in value-based decision making and how links to psychological resilience are related to individual differences in cognitive and neural processing of reward and punishment signals. In a cost-benefit integration task, 82 participants (41 female, 41 male human subjects) weighed gains and losses associated with different features (color, shape) of compound visual stimuli. A positive choice bias in decision making was associated with trait acceptance as a facet of self-reported resilience—and this cross-sectional link was statistically mediated by differences in the neural processing of value information as measured with fMRI: Participants with a more positive choice bias and higher trait acceptance showed stronger increases in neural activity in response to negative information (loss) in 10 prefrontal and parietal brain regions—and stronger decreases in response to positive information (gain) in the right inferior frontal junction. Cognitive-computational modeling revealed that more positive choice biases were associated with lower sensitivity to and valuation of negative relative to positive information. Notably, higher valuation of positive information was associated with stronger neural responses to negative information in dACC and insula. Finally, choice bias and trait acceptance were associated with functional connectivity between prefrontal seeds, midbrain, striatum, and ventromedial prefrontal cortex. The stronger activation of brain regions associated with cognitive control, specifically for negative information, suggests a stronger regulatory influence on the processing of negative information, potentially promoting a positive choice bias that is able to support resilience.

Author Correction: The role of harmonicity on listeners’ ability to hear out voices in polyphonic music

Primary results of the BETTER-CARE trial: Implementation of a needs-adapted and individualized follow-up care after primary breast cancer.

LBA510 Background: Follow-up care after primary breast cancer is a central component of oncological care and is gaining importance in light of increasing survival rates. In addition, an increasing variety of adjuvant treatment concepts with differing toxicities exists and individual physical, psychological, and social consequences of the disease and its treatment are receiving greater attention. However, internationally standardized follow-up care only partially meets these heterogeneous and dynamic needs. The aim of this study was to evaluate a needs-adapted follow-up care concept within the framework of a cluster intervention study. Methods: BETTER-CARE is a parallel-arm controlled trial with 30 clusters (certified Breast Cancer Centers) across Germany randomized 1:1, that was funded by the Federal Joint Committee (G-BA, grant 01NVF20015). Breast cancer patients of all genders aged 18 years or older no later than 10 weeks after completion of curative primary treatment with informed consent were included. The needs- and risk-adapted complex intervention comprised a multidisciplinary care network, digital platforms and just-in-time adaptive interventions. The control group received usual care defined by clinical guidelines. The primary endpoint was health-related quality of life (HRQoL, EORTC QLQ-C30 global health) at 12-month. Secondary endpoints included treatment adherence, late effects and psychiatric comorbidities, among others. To detect an effect with a power of 90% and a significance level of 5%, a sample size of 570 patients per arm was planned. Linear univariable and multivariable mixed-effects models were applied adjusting for respective baseline values, age, molecular subtype, BRCA detection and Charlson-Comorbidity-Index. Results: Between 2023 and 2025, 30 clusters were randomly assigned to the intervention (n=15) or control group (n=15), no cluster dropped out. 338 of 410 patients in the intervention and 445 of 523 in the control group were included in the modified ITT analysis (data on primary endpoint available). At follow-up there was no significant difference in HRQoL (adjusted Odds Ratio (aOR): 1.61 (95%-CI: -1.4-4.62)). The intervention group showed significantly lower proportions of fatigue (18.3% vs 24.4%, aOR: 0.57 (95%-CI: 0.37-0.86)), depression (11.3% vs 19.3%, aOR 0.46 (95%-CI: 0.28-0.75)), cognitive impairment (35.5% vs 47.5%, aOR: 0.52 (95%-CI: 0.38-0.71)), neurotoxicity (40.8% vs 50.3%, aOR: 0.68 (95%-CI: 0.5-0.93)) and restrictions in daily activities (42.3% vs 50.1%, aOR: 0.65 (95%-CI: 0.48-0.88)). No differences were identified for the remaining secondary endpoints. Conclusion: No differences were identified between the intervention and control group regarding the primary endpoint HRQoL. Positive effects regarding psychiatric comorbidities, late side effects and activities in daily living were found in the intervention group. Implementing this complex intervention can be particularly useful for improving neuropsychiatric outcomes. Clinical trial information: DRKS00028840.

Anomer-Selective Vorbrüggen Reaction for the Catalytic Synthesis of C ₂ -Deoxynucleoside Analogues

Histamine Originating from the BNST Modulates Corticostriatal Synaptic Transmission during Early Postnatal Development

The neuromodulator histamine regulates key processes in many circuits of the adult and developing brain, including striatum. However, striatal innervation by histaminergic afferents is very sparse making the physiological sources of histamine unclear. Here sources of striatal histamine were investigated during early postnatal development and specifically during the second postnatal week in mice of either sex. Firstly, a combination of patch-clamp recording and optogenetic stimulation in brain slices demonstrates that during this period exogenously applied histamine modulates both the intrinsic properties of developing D 1 and D 2 striatal spiny projection neurons (SPNs) and synaptic transmission at afferents coming from the mPFC and visual cortex. Secondly, immunohistochemistry for histamine reveals a brain region adjacent to the caudal striatum densely innervated by histaminergic axons and corresponding to the oval nucleus of bed nucleus of stria terminalis (ovBNST). Thirdly, electrical stimulation of the ovBNST leads to significant and detectable levels of histamine in striatum, as assessed by fast scan cyclic voltammetry and fluorescent histamine sensors in brain slices as well as in vivo. Lastly, electrical stimulation of the ovBNST nucleus, at frequencies mimicking normal active histamine neurons, can release sufficient levels of histamine to modulate excitatory synaptic transmission from mPFC onto striatal SPNs through histamine H 3 receptors. Together, these results provide evidence for the existence of the ovBNST as an extrastriatal source of histamine during early brain development and postulates a new view of the modus operandi of histamine in that it can cross anatomical and functional boundaries and act as a paracrine neuromodulator.

A smiling mouth expression modulates gaze appearance by enhancing how the eyes light up

Abstract Research on composite facial expressions has shown that a smiling mouth, when combined with neutral eyes, can influence how the eyes are interpreted. From a gestalt-oriented perspective, we propose that smiling not only affects emotion recognition but also produces a fascinating, compelling visual counterpart: an enhancement of the eyes’ apparent luminosity, or ‘lighting up’. We tested this hypothesis in two within-subject experiments by collecting ratings of perceived eye brightness and smile intensity for whole faces, as well as for eyes and mouths presented isolated. In Experiment 1, we combined neutral eyes with neutral, slightly smiling, and fully smiling mouths. Results show that, for each stimulus, eye brightness ratings increased as a function of smile intensity. In Experiment 2, we combined neutral and Duchenne-smiling eyes with neutral and smiling mouths. Data analysis reveals that a smiling mouth significantly enhances the luminosity ratings of Duchenne-smiling eyes compared to their own perceptual baseline (individual eyes presented alone). Furthermore, a neutral mouth appears to ‘dim’ the brightness of Duchenne-smiling eyes. Through further pictorial demonstrations, we suggest that this phenomenon is remarkably robust, occurring in naturalistic photographic portraits, pareidolic faces and paintings. We propose that this subtle yet compelling effect represents a perceptual signature of the gaze, intensifying facial aliveness as the mouth modulates the eyes’ appearance. Mirroring the relational logic of the Wollaston illusion, our findings demonstrate that the eyes and mouth operate in synergy, forming a unified expression where the visual system integrates individual features into a harmonious and living whole.

Neoadjuvant rilvegostomig (R) + trastuzumab deruxtecan (T-DXd) in high-risk HER2-negative breast cancer: Results from the I-SPY 2.2 trial.

LBA514 Background: Preclinical and clinical data show that antibody-drug conjugates (ADCs) such as T-DXd may synergize with immunotherapy. Rilvegostomig (R) is a monovalent, Fc-reduced, dual checkpoint bispecific IgG1 monoclonal antibody against PD-1 and TIGIT receptors. R + T-DXd was evaluated as neoadjuvant therapy for up to 4 cycles. Methods: I-SPY2.2 is a phase II neoadjuvant trial with three neoadjuvant sequences (Blocks A/B/C). All HER2-negative subtypes were eligible for R + T-DXd in Block A. Predicted responders at the end of Block A or B could undergo surgery; otherwise, they continued to Block B +/- C. Block B pts received paclitaxel +/- carboplatin +/- pembrolizumab and Block C pts doxorubicin + cyclophosphamide (AC) +/- pembrolizumab, HR+ immune+ received IO in Blocks B/C. Results are analyzed by receptor and response predictive subtypes (RPS), that include expression-based immune, and luminal signatures with hormone receptor (HR) and HER2 status. Some pts were randomized to a control regimen (skipping R + T-DXd in block A and starting in block B). To minimize risk of interstitial lung disease (ILD) that could lead to treatment discontinuation, pts underwent pulmonary function tests and high-resolution chest CTs every 6 weeks. Abnormalities were reviewed in real time. The primary endpoint was pathologic complete response (pCR), within each RPS and HR/HER2 signature, with estimated pCR (EpCR) rates compared to subtype-specific block A goal rates and control pts in those groups. Other endpoints included safety and treatment discontinuation. Results: 105 pts were treated with R + T-DXd in block A, while 31 pts were randomized to the control regimen. Block A EpCR rate was 57% in the 12 HR+Immune+ pts vs a pre-specified goal of 15% (posterior probability, PP > .99). In 35 HR-Immune+ pts EpCR was 52% vs a pre-specified goal of 40% (PP = .87). No other groups (Immune-) had a PP > .85 for their respective pCR goal rate. HER2-IHC was 0 (27.6%), 1+ (49.5%) and 2+ (22.9%) in the treatment arm vs. 37.7%, 37.7%, and 24.7% in the control arm, with no difference in distribution between arms in immune subtypes. The most common adverse events in Block A were fatigue (84.8%), nausea (81.0%) and alopecia (58.1%). ILD was the most common adverse event of special interest in Block A and overall, occurring in 12 pts (11.4%; 7G1, 4G2, 1G3) during Block A and in 3 pts (G1, 2.9%) in other Blocks. 8 pts discontinued T-DXd + R due to ILD and proceeded to the next Block. Conclusions: When considering the full treatment strategy including block B and C regimens, experimental strategies had similar EpCR rates vs. controls in immune+ subtypes but block A rates exceeded pre-defined goal thresholds. This infers that treatment beginning with R + T-DXd has equivalent efficacy to standard of care for immune+ pts, but 64% pts with pCR skip chemotherapy (Block B) and 97% avoid AC (Block C). R + T-DXd participants avoided persistent ILD. Clinical trial information: NCT01042379 .

Clinicoradiological differentiation of TERT promoter-mutant molecular glioblastoma versus histological glioblastoma: a single-center cohort study of 105 IDH-wildtype tumors

Omission of completion axillary dissection in patients with breast cancer and sentinel lymph node macrometastases: Overall survival and patient-reported arm morbidity from the randomized SENOMAC trial.

LBA503 Background: Axillary lymph node dissection (ALND) causes arm-related morbidity. The SENOMAC trial evaluates whether the omission of completion ALND in patients with 1-2 sentinel lymph node (SLN) macrometastases is oncologically safe. It differs from previous trials in size and the inclusion of larger tumors and patients receiving mastectomy. Methods: SENOMAC (NCT02240472) is an international non-inferiority trial. Adult patients with primary invasive, clinically node-negative T1-3 breast cancer and up to two SLN macrometastases were randomized 1:1 to completion ALND (standard) or its omission (intervention). Adjuvant treatment followed standards of care. The primary endpoint was overall survival (OS), requiring 190 deaths to conclude non-inferiority (upper one-sided 90% CI for the hazard ratio < 1.44) with ALND as the reference group. The secondary endpoint breast cancer-specific survival (BCSS) required 66 breast cancer deaths. Patient-reported outcomes were recorded 1, 3, and 5 years after randomization by the questionnaires Lymph-ICF (arm morbidity), EORTC QLQ-C30 and BR23 (health-related quality of life). Results: From 1/2015 to 12/2021, 2766 patients were randomized in 5 countries. The per-protocol population comprised 2540 patients (1205 randomized to ALND and 1335 to its omission). The median follow-up was 60.1 months (1.5-122.7 months). Questionnaire response rates were 81.3% and 74.6% at 3 and 5 years, respectively. Overall, 196 patients died, 75 of whom due to breast cancer. Five-year OS was 93.4% (95% CI 91.9%-94.9%) in the ALND and 94.4% (95% CI 93.1%-95.7%) in the omission group, with a country-adjusted hazard ratio of 0.84 (95% CI 0.64-1.12). Five-year BCSS was 97.3% (95% CI 96.4%-98.3%) in the ALND and 97.8% (95% CI 97.0%-98.6%) in the omission group, with a country-adjusted hazard ratio of 0.86 (95% CI 0.55-1.34). Both endpoints fell significantly (p = 0.238 for OS and p = 0.504 for BCSS) below the pre-specified non-inferiority margin. Arm physical function according to the Lymph-ICF questionnaire was significantly better in the omission than the ALND group with a clinically relevant mean score difference of 6.14 at 3 years (95% CI 5.00-7.43, p < 0.001) and 5.71 at 5 years (95% CI 4.46-7.25, p < 0.001). Similarly, arm symptoms according to EORTC QLQ-BR23 were significantly more pronounced in the ALND than the omission group both after 3 (mean score 20.80+/-21.24 versus mean score 10.83+/-15.48, p < 0.001) and after 5 years (mean score 19.40+/-21.07 versus mean score 9.31+/-15.58, p < 0.001). Global health-related quality of life did not show any statistically significant differences after 3 and 5 years. Conclusions: Omission of completion ALND after a positive SLN biopsy is oncologically safe and mitigates postoperative patient-reported arm morbidity. Clinical trial information: NCT02240472 .