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Synergistic Effect of Combination Treatment of Brexpiprazole and Nalmefene on Ethanol Intake in Rats

Neuropsychopharmacol Rep. 2026 Mar;46(1):e70107. doi: 10.1002/npr2.70107.

ABSTRACT

AIMS: Reduction of alcohol consumption is one of treatment goals to reduce harm among individuals with alcohol use disorder (AUD), a major worldwide health problem, for which nalmefene, an opioid receptor modulator, is used. In this study, the effect of nalmefene on ethanol (EtOH) intake, already reported, was evaluated in Wistar rats, as validation. In addition, effects of brexpiprazole, serotonin-dopamine activity modulator, alone and in combination with nalmefene were evaluated to investigate further treatment option for AUD.

METHODS: During the first training phase, animals had 10% EtOH as the only drinking fluid available for the first 5 days. Then, the animals had a 24-h free choice between EtOH and water for 39 days which is named the continual access paradigm. Thereafter, the limited access paradigm, which restricted the availability of 10% EtOH to 1 h every day, was carried out for 114 days. EtOH intake (g/kg/1 h) was determined by weighing 10% EtOH bottles before and after the limited EtOH access every day. Brexpiprazole (0.01-0.1 mg/kg, orally) and nalmefene (0.04-0.4 mg/kg, subcutaneously) were daily administered to rats 1 h or 20 min before starting the limited access paradigm for consecutive 4 days, respectively. The combination effect was evaluated using each subeffective dose of brexpiprazole and nalmefene which did not significantly reduce EtOH intake. The daily and the average EtOH intake for 4 days before and during the treatment with test compounds were statistically analyzed.

RESULTS: Brexpiprazole (0.1 mg/kg) and nalmefene (0.4 mg/kg) alone significantly decreased EtOH intake. Moreover, the combination of subeffective doses of brexpiprazole (0.01 mg/kg) and nalmefene (0.04 mg/kg) significantly and synergistically decreased EtOH intake.

CONCLUSION: These data suggest that brexpiprazole may have the potential to decrease alcohol intake in AUD patients. In addition, brexpiprazole may have a synergistic therapeutic effect with nalmefene in those patients.

PMID:41793049 | DOI:10.1002/npr2.70107

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CHO Cell Line Selection through Multi-Criteria Analysis Reveals Critical Impact of Gas Overlay

Biotechnol J. 2026 Mar;21(3):e70206. doi: 10.1002/biot.70206.

ABSTRACT

The development of robust Chinese Hamster Ovary (CHO) cell lines expressing high titers of monoclonal antibodies (MAbs) is central to bioprocess development. Following transfection and pool generation, clone selection is critical, as individual clones often behave differently in stirred-tank bioreactors. We propose a multivariate data analysis (MVDA) approach for clone selection that integrates productivity, growth, expression stability, and metabolism, with adaptable weighting based on process priorities. This method was applied to in-house data from CHO clones producing omalizumab. From 24 candidates, eight stable, high-performing clones were advanced for evaluation in 0.75-1 L bioreactors. MVDA revealed that including stability and metabolic parameters alters the ranking of lead clones compared with conventional screening. To assess scalability, cultures were run with or without air overlay to modulate dissolved CO2. Cultures without overlay reached up to 25% pCO2 (190 mmHg) and unexpectedly showed improved performance: 1.69-fold higher titer, 1.43-fold greater cell-specific productivity, 1.11-fold higher peak cell density, extended viability, and sustained product accumulation over 17-21 days. By integrating statistical tools and a historical dataset, our MVDA method identified a robust lead clone performing consistently across CO2 conditions, supporting its application in early upstream bioprocess development.

PMID:41793045 | DOI:10.1002/biot.70206

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Neoplastic Foot Ulcers: A Multicentre Retrospective Study

Int Wound J. 2026 Mar;23(3):e70871. doi: 10.1111/iwj.70871.

ABSTRACT

Neoplastic foot ulcers are particularly challenging for dermatologists and specialists in hard-to-heal wounds because their location and comorbidities can delay accurate diagnosis. We performed a multicentre, retrospective study analysing clinical and histological data, focusing on neoplastic foot ulcers collected over the past 5 years. We evaluated patients’ demographic characteristics, clinical features, histological diagnosis, tumour onset and ulcer site. Statistical analyses were conducted using SPSS software, v.30. In total, 106 patients affected by foot skin ulcers were enrolled in the present protocol (52 women, 54 men). The mean age was 70.15 years. In most cases, the neoplastic ulcer was due to primary tumour ulceration. The dorsum of the foot was the most common site of neoplastic ulcers (66%). From a clinical perspective, most lesions were classified as ulcerated nodules (n = 58), ulcerated plaques (n = 8) or hypergranulating ulcers (n = 25), all with thickened, atypical edges. Histological diagnoses included melanoma (n = 45), non-melanoma skin cancers (n = 34), benign tumours (n = 18) and rarer malignancies (n = 9). A statistically significant correlation was found between histotype and clinical lesion type, and between age and histotype. The study provided preliminary data on the clinical and histological characteristics of neoplastic foot ulcers, warranting further exploration in a prospective, multicentre study.

PMID:41793027 | DOI:10.1111/iwj.70871

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Results of the Use of Platelet-Rich Plasma in the Donor Site of Split-Thickness Skin Grafts: An Exploratory Cohort Study

Int Wound J. 2026 Mar;23(3):e70852. doi: 10.1111/iwj.70852.

ABSTRACT

Split-thickness skin autografts are commonly used to treat extensive cutaneous defects. However, donor site morbidity, including pain, bleeding, and delayed epithelialization, remains a major clinical challenge. This study evaluates whether applying autologous platelet-rich plasma (PRP) to the donor site improves healing outcomes. A prospective cohort study was conducted at a tertiary-level academic hospital in Colombia. The study protocol was approved by the local Institutional Ethics Committee. Adult patients (> 18 years) undergoing split-thickness skin grafts for trauma, burns, oncologic resections, or chronic ulcers were included. Two groups were compared: the PRP group, in which autologous platelet-rich plasma was applied to the donor site, and the control group, which received standard wound care. The primary outcome was the quality of epithelialization at the donor site, while pain, assessed using the Numeric Rating Scale, was evaluated as a secondary outcome at multiple postoperative time points. Data were analysed using descriptive statistics and linear mixed-effects models adjusted for potential confounders, with statistical significance set at p < 0.05. A total of 46 patients were included (16 in the PRP group and 30 in the control group), with no significant demographic differences between groups. The PRP group demonstrated improved epithelialization quality, with lower Vancouver Scar Scale scores on postoperative days 7 and 14 (p < 0.05). Patients treated with PRP also reported a reduction of up to 50% in postoperative pain during early assessments (p < 0.001). These effects were maintained throughout the follow-up period, suggesting a sustained benefit of PRP on both healing quality and pain control. These findings suggest that autologous PRP application at split-thickness skin graft donor sites may enhance early epithelialization quality and reduce postoperative pain compared with standard wound care. PRP appears to be safe and may represent a useful adjunct to promote improved wound healing and patient recovery in reconstructive surgery. However, larger randomised controlled trials are required to confirm these findings and to establish the clinical effectiveness of autologous PRP in this setting.

PMID:41793011 | DOI:10.1111/iwj.70852

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Single-qubit graph classifier with classical feature aggregation

Neural Netw. 2026 Feb 26;200:108775. doi: 10.1016/j.neunet.2026.108775. Online ahead of print.

ABSTRACT

In this paper, we propose a single-qubit graph classifier that combines classical graph representation with quantum computing. Through a lightweight architecture, it achieves flexible and efficient graph data processing. This model delegates the task of aggregating node features that do not require inference to a classical subroutine, and optimizes the key weight training process with quantum programs, thereby constructing a basic graph classifier that uses only one qubit. Experimental results show that in binary classification tasks, the proposed single-qubit classifier demonstrates strong competitiveness in terms of performance when compared with traditional algorithms and quantum algorithms. Additionally, we utilize a parallel training scheme for multiple single-qubit classifiers to effectively enhance performance in multi-classification tasks. Evaluations conducted in different quantum noise simulation environments indicate that the proposed model has good robustness, and the parallel training scheme for multiple classifiers further enhances the model’s robustness in multi-classification tasks. More importantly, this model can be flexibly combined with various classical graph neural networks, providing a way to promote the application of quantum graph neural networks in diverse scenarios.

PMID:41791178 | DOI:10.1016/j.neunet.2026.108775

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Image segmentation algorithm based on the Allen-Cahn energy function

Neural Netw. 2026 Mar 1;200:108753. doi: 10.1016/j.neunet.2026.108753. Online ahead of print.

ABSTRACT

In this paper, we introduce a novel algorithm for image segmentation, which is based on the Allen-Cahn (AC) energy function. Our methodology involves calculating the energy feature at a local level in an image by means of the sliding window technique on the image matrix, which ultimately produces the energy matrix necessary for segmenting the image. Subsequently, constraints are constructed using the extreme values in the energy matrix. By varying the parameters in the constraints and the size of the sliding window, image segmentation results are obtained for different demand purposes. This paper empirically analyzes various simple and complex images, demonstrating the algorithm’s effectiveness in segmentation across different complexities and its excellent performance in agronomy and medicine. We also compare our method with other state-of-the-arts and our algorithm exhibits significant advantages in terms of time-saving. In order to further optimise the parameter selection process, we improve the algorithm so that it can autonomously output the parameters that make the segmentation results optimal. Additionally, we conduct experiments on several classical image segmentation datasets, as well as evaluating the segmentation results through the introduction of evaluation metrics, to demonstrate the effectiveness and applicability of our optimised algorithm. Our method demonstrates outstanding performance in image segmentation experiments on the CO-SKEL dataset, with an average segmentation time of 0.2 s. The accuracy exceeds 95%, and precision, recall, and F1 scores all surpass 90%. Even under various noise interferences, the segmentation accuracy of the algorithm remains above 94%, highlighting its efficiency and robustness.

PMID:41791175 | DOI:10.1016/j.neunet.2026.108753

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Efficacy and Safety Outcomes of Stereotactic Radiotherapy With Cyberknife System in Brain Metastases Patients Treated With Immunotherapy or Targeted Therapy

Clin Oncol (R Coll Radiol). 2026 Feb 14;52:104084. doi: 10.1016/j.clon.2026.104084. Online ahead of print.

ABSTRACT

AIMS: Brain metastases (BMs) represent the most common intracranial tumours in adults with advanced solid cancers, significantly impacting morbidity and mortality. While the emergence of systemic therapies such as immunotherapy (IT) and targeted therapy (TT) has improved survival outcomes, the interaction of these modalities with stereotactic radiotherapy/radiosurgery (SRS/SRT) remains poorly explored. This study aims to evaluate the safety, local control (LC), and efficacy of combining SRS/SRT with IT or TT in patients with BM.

MATERIALS AND METHODS: This prospective, monocentric study (“RaBITT Trial”) analysed patients with BM treated with SRS/SRT using the CyberKnife system (Accuray) between May 2020 and May 2023. Patients received IT or TT in conjunction with SRS/SRT. Outcomes assessed included LC, overall survival (OS), disease-free survival (DFS), and next-line systemic treatment-free survival (NEST-FS). Toxicity, including radionecrosis and haemorrhage, was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Statistical analysis employed Kaplan-Meier curves and univariate (UVA) and multivariate (MVA) regression models.

RESULTS: We analysed 45 patients with a total of 225 BMs. The LC rate at 1 and 2 years was 85.7% and 79.8%, respectively. The overall response rate was 85.3%, with 56 complete responses (CRs). Multivariate analysis identified a higher biological effective dose with an α/β ratio of 10 and prescription isodose as predictors of CR. DFS rates at 1 and 2 years were 37.1% and 27.5%, respectively, while OS rates were 52.5% and 44.7%, respectively. NEST-FS rates at 1 and 2 years were 35.9% and 25.5%, respectively. Toxicity analysis revealed a radionecrosis rate of 20% for patients (6.7% of total lesions), with most cases being asymptomatic. Intralesional haemorrhage occurred in 1.7% of lesions, predominantly in melanoma and lung cancer patients.

CONCLUSION: The combination of SRS/SRT with IT or TT yields high rates of LC and overall response with a manageable safety profile, emphasising the importance of personalised dosimetric planning and careful toxicity monitoring. Despite promising outcomes, the study’s monocentric nature and limited sample size highlight the need for multicenter trials with extended follow-up to optimise treatment strategies and better understand long-term risks and benefits.

PMID:41791143 | DOI:10.1016/j.clon.2026.104084

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Influence of predominant back versus leg pain on clinical outcomes in unilateral biportal endoscopic lumbar decompression

J Neurosurg Spine. 2026 Mar 6:1-9. doi: 10.3171/2025.9.SPINE241288. Online ahead of print.

ABSTRACT

OBJECTIVE: Limited research has explored the impact of predominant back pain (pBP) versus predominant leg pain (pLP) in patients undergoing unilateral biportal endoscopic lumbar decompression (UBE-LD). This study aimed to evaluate and compare the perioperative and postoperative clinical outcomes, using patient-reported outcome measures (PROMs) and minimal clinically important difference (MCID), between patients with pBP and pLP who underwent UBE-LD.

METHODS: Patients who underwent primary UBE-LD were divided into either the pBP or pLP cohort. Exclusion criteria included patients with a diagnosis of degenerative scoliosis, trauma, malignancy, or infection. Demographic, perioperative characteristics, PROMs, and MCID were compared between cohorts using inferential statistics. PROMs were collected at preoperative and postoperative 6-week, 12-week, and 6-month time points. Assessed PROMs included the Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), Veterans Rand 12-Item Health Survey (VR-12) physical component score (PCS), VR-12 mental component score (MCS), visual analog scale (VAS) for back pain, VAS for leg pain, and Oswestry Disability Index (ODI). MCID attainment was determined by comparing the change in PROMs to established thresholds in the literature.

RESULTS: A total of 98 patients were included in the study, with 52 in the pBP cohort and 46 in pLP cohort. After analysis, there were no significant differences in baseline demographic or perioperative characteristics between the two groups. The majority of patients had a diagnosis of herniated nucleus pulposus (81.6%), central stenosis (93.9%), and foraminal stenosis (77.6%). At 6 months, both cohorts experienced significant postoperative improvements in PROMIS-PF, VAS back pain, VAS leg pain, VR-12 PCS, and ODI scores (all p ≤ 0.011). VR-12 MCS scores did not demonstrate sustained postoperative improvement in either cohort. High rates of MCID achievement were observed across both cohorts for multiple PROMs, with no statistically significant differences in MCID attainment between patients with pBP and pLP at any postoperative time point.

CONCLUSIONS: Regardless of the preoperative predominant pain location, patients undergoing UBE-LD reported significant improvements in physical function, back and leg pain, and disability. Patients in both cohorts demonstrated improvements in mental health outcomes, with comparable MCID achievement rates for VR-12 MCS. These findings suggest that UBE-LD might be effective for patients with both predominant back and leg pain presentations, although differences in specific outcome domains should be interpreted with caution due to potential selection bias. Consideration of predominant pain location might help inform preoperative patient counseling regarding expected outcomes following UBE-LD.

PMID:41791117 | DOI:10.3171/2025.9.SPINE241288

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Factors affecting cognitive status in patients with intracranial atherosclerosis after surgical revascularization: a post hoc analysis of the ERSIAS-PC phase II trial

J Neurosurg. 2026 Mar 6:1-6. doi: 10.3171/2025.10.JNS251032. Online ahead of print.

ABSTRACT

OBJECTIVE: Patients experiencing ischemic strokes typically develop substantial cognitive decline. Intracranial atherosclerotic disease (ICAD) is a common stroke etiology that exposes patients to high and prolonged risks of recurrence. The ERSIAS-PC (Encephaloduroarteriosynangiosis revascularization for symptomatic intracranial atherosclerotic steno-occlusive performance criterion) phase II trial showed a lower risk of recurrent stroke in patients who underwent encephaloduroarteriosynangiosis (EDAS) plus intensive medical management (IMM). In the current study, the authors evaluate factors contributing to cognitive decline in patients with symptomatic ICAD treated with EDAS revascularization.

METHODS: ERSIAS-PC patients without aphasia who had completed at least 1 year of follow-up were included this post hoc analysis. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) at baseline and each follow-up and was classified as improved/preserved or worsened. Classification and regression tree (CART) analysis was used to identify factors associated with changes in cognitive function. The factors considered were age, sex, stenosis versus occlusion, baseline modified Rankin Scale score, good collateralization, and compliance with diabetes mellitus (DM), hypertension, and hyperlipidemia (HLD) treatments.

RESULTS: Of the 52 ERSIAS-PC patients, 39 were included in this subgroup analysis. The median age was 46 (IQR 37.0-56.0) years, and 27 (69.2%) patients were female. The mean MoCA score was 22.4 ± 4.9 at baseline and 23.9 ± 4.9 at the 1-year follow-up among the 52 patients in the ERSIAS-PC trial population. Among the 39 patients in this subgroup analysis, the MoCA score improved or remained stable in 33 (84.6%) and declined in 6 (15.4%). CART analysis indicated that the most relevant factor for an improved MoCA score after surgery was compliance with DM treatment (94.5% yes vs 74.2% no, p = 0.02). Other factors indicating a nominal though not statistically significant influence were HLD treatment (83.3% yes vs 60.5% no, p = 0.2) and stenosis (99.1% vs 80.9% occlusion, p = 0.6).

CONCLUSIONS: Compliance with DM treatment was significantly associated with cognitive preservation in patients with symptomatic ICAD treated with EDAS. The study findings emphasize the importance of the IMM of stroke risk factors in patients with intracranial atherosclerosis, even after surgical revascularization.

PMID:41791115 | DOI:10.3171/2025.10.JNS251032

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Febrile Seizures in an App-Based Children’s Fever Registry: Mixed Methods Study

JMIR Pediatr Parent. 2026 Mar 6;9:e74933. doi: 10.2196/74933.

ABSTRACT

BACKGROUND: Febrile seizures, although typically benign, can cause significant emotional distress for parents. Their diverse etiological risk factors underscore the need for further research. Ecological momentary assessment (EMA) offers a cost-effective and timely method for real-time data collection. The FeverApp, an EMA-based registry for fever management, enables parents to document febrile seizures as they occur.

OBJECTIVE: This study systematically investigates febrile seizure records from the FeverApp registry to assess their characteristics and explore the clinical implications of the findings. By providing real-world data on seizure management, this research demonstrates the potential of app-based EMA in pediatric care. Additionally, it offers insights for targeted interventions and improved febrile seizure management.

METHODS: We used a mixed methods approach. A descriptive qualitative analysis of parental descriptions of 226 seizures belonging to 161 children was conducted. Additionally, a comparative quantitative analysis of group differences was assessed through matched-pair sampling, comparing 114 children. Statistical methods were tailored to the nature of the respective variables, which included prevalence, age, gender, health and febrile history, fever management, temperature, well-being, and parental confidence.

RESULTS: Qualitative analyses provided detailed descriptions of seizure symptoms, seizure duration, and seizure management practices. Additionally, the data revealed a high rate of emergency consultations related to febrile seizures. However, there was underreporting of febrile seizures within the FeverApp, with a reported incidence of only 0.4% among febrile children. In a matched sample controlled for gender and age, significant differences were observed between febrile children with and those without febrile seizures in several parameters, including maximum recorded temperature (P<.001), prevalence of chronic diseases (P=.004), parental confidence (P=.01), and frequency of emergency consultations (P<.001).

CONCLUSIONS: This study offers valuable insights into the characteristics, temporal dynamics, management strategies, and parental responses to febrile seizures in children. Despite the limitation of potential underreporting in an EMA-based registry, the findings highlight the critical importance of parental education and support in managing febrile seizures. Enhancing these areas has the potential to reduce unnecessary medical consultations and improve the overall care of affected children. Furthermore, integrating improvements in the FeverApp’s education and documentation system regarding febrile seizures could facilitate better management and support future research efforts.

PMID:41791112 | DOI:10.2196/74933