Search Results (3,443)

Extensive research is being carried out on the application of $\alpha$ particles for cancer treatment. A key challenge in $\alpha$ therapy is how to deliver the $\alpha$ emitters to the tumour. In AlphaGlue, a novel treatment delivery concept, the $\alpha$ emitters are suspended in a thin layer of glue that is put on top of the tumour. In principle, this should be an easy and safe way to apply $\alpha$ therapy. In this study, the effectiveness of AlphaGlue is evaluated using GEANT4 and GEANT4-DNA simulations to calculate the DNA damage as a function of depth. Two radionuclides are considered in this work, ²¹¹At and ²²⁴Ra. The results indicate that, as a concept, the method offers a promising hypothesis for treating superficial tumours, such as skin cancer, when ²²⁴Ra is applied directly on the tissue and stabilized with a glue layer. This results in 2$\times {10}^{-5}$ complex double strand breaks and 5$\times {10}^{-5}$ double strand breaks at 5 mm depth per applied ²²⁴Ra atom. When applying a ²²⁴Ra atom concentration of $(4.35\pm 0.2)\times {10}^{11}/$cm² corresponding to an activity of $(21.8\pm 1)\mathsf{\mu }$Ci/cm² on the skin surface, the RBE weighted dose exceeds 20 Gy at 5 mm depth. Hence, there is significant cell death at 5 mm into the tissue; a depth matching clinical requirements for skin cancer treatment. Given the rapidly falling weighted dose versus depth curve, the treatment depth can be tuned with good precision. The results of this study show that AlphaGlue is a promosing treatment and open the pathway towards the next stage of the research, which includes in-vitro studies. Full article

Varroa mites are a major global threat to honeybee colonies. Combining digital twins with scenario-generating models can be an enabler of precision apiculture, allowing for monitoring Varroa spread, generating treatment scenarios under varying conditions, and running remote interventions. This paper presents the conceptual design of this system for large-scale Varroa management in honeybee apiaries, with initial validation conducted through simulations and feasibility analysis. The design followed a design research framework. The proposed system integrates a wireless sensor network for continuous hive sensing, image capture, and remote actuation of treatment. It employs generative time-series models to forecast colony dynamics and a statistical network model to represent inter-colony spread; together, they support spread scenario prediction and what-if evaluations of treatments. The system evolves through continuous updates from field data, improving the accuracy of spread and treatment models over time. As part of our design research, an early feasibility assessment was carried out through the generation of synthetic data for spread model pretraining. In addition, a node-level energy budget for sensing, communication, and in-hive treatment was developed and matched with battery capacity and life calculations. Overall, this work outlines a path toward real-time, data-driven Varroa management across apiary networks, from regional to cross-border scales. Full article

Background: The core management of most individuals with asthma and COPD is daily treatment with inhalers such as inhaled corticosteroids (ICS) and long-acting bronchodilators. The two main types of inhalers used are pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Different studies have shown low adherence to inhaler treatments among subjects with asthma and COPD. In this study, we explored the differences in adherence between pMDIs and DPIs of combined ICS and long-acting β₂-agonist inhalers (ICS + LABA) in a large cohort, free from commercial biases. Methods: In this historical prospective study, we included all adult subjects with asthma and/or COPD who acquired at least one ICS + LABA inhaler between 2016 and 2019. We carried out propensity score matching and then compared the maximal number of pMDIs and DPIs purchased in any continuous 12 months during the study period. We also compared once-a-day DPIs with twice-a-day DPIs. Results: Of the 36,998 matched subjects, 5897 (15.9%) purchased pMDIs. The overall median [IQR] inhalers purchased for pMDIs and DPIs were 1 [1, 4] and 3 [1, 8], respectively; for subjects with asthma, 1 [1, 3] and 2 [1, 6]; for subjects with COPD, 1 [1, 3] and 3 [1, 10]; and for subjects with asthma–COPD overlap, 2 [1, 7] and 6 [2, 12]. For all the comparisons, p < 0.001. The once-a-day DPI group had a slight but significantly better adherence than the twice-a-day DPI group. Conclusions: For ICS + LABA therapy, the number of DPIs purchased was significantly greater than the number of pMDIs purchased, as well as the once-a-day DPI relative to the other DPIs. Overall, subjects with asthma and/or COPD had low adherence to all inhalers, with the highest adherence observed among subjects with asthma–COPD overlap. Full article

Background/Objectives: Decompressive craniectomy (DC) is commonly applied to manage refractory intracranial hypertension in severe traumatic brain injury (TBI). However, its role and benefits in pediatric populations remain uncertain. Clarifying whether DC provides measurable clinical advantages in children with severe TBI may inform treatment strategies and family counseling. Methods: We conducted a retrospective, one-to-one matched cohort study at a tertiary pediatric center (2014–2023). Fifty-three children with severe TBI who underwent DC were matched with fifty-three non-DC patients based on age, Glasgow Coma Scale score, cranial CT findings, and pupillary response at admission to ensure comparable injury severity. Demographic data, clinical features, and outcomes were collected. Primary outcomes were in-hospital mortality and Pediatric Cerebral Performance Category (PCPC) scores at discharge and 3 months. Secondary outcomes included duration of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay. Results: Mortality did not differ significantly between DC and non-DC groups (17.0% vs. 26.4%, p = 0.239). DC patients had better PCPC scores at discharge (p = 0.029). At 3 months, the between-group difference was not statistically significant but showed a near-significant trend (p = 0.057). No significant differences were observed in duration of ventilation (p = 0.100), ICU stay (p = 0.348), or hospital stay (p = 0.678). Conclusions: DC may not reduce short-term mortality in pediatric severe TBI but appears to be associated with more favorable neurological outcomes at discharge. Larger, adequately powered studies with standardized monitoring and longer follow-up are needed to clarify the durability and scope of potential benefits in this population. Full article

Objectives: This study aimed to assess the impact of traditional Korean medicine services (TKMS) on subsequent knee surgery and opioid use in patients diagnosed with knee osteoarthritis (KOA). Methods: This retrospective cohort study used National Health Insurance Review and Assessment Service claims data from 2015 to 2017 to identify patients treated for KOA (M17) in 2016. Patients with at least two Korean medicine (KM) clinic visits within 6 weeks of the initial diagnosis formed the TKMS group, while those without visits to KM clinics formed the n group. Propensity score matching (PSM) (1:1) was applied and the incidence of knee surgery and opioid use was followed up for one year. Kaplan–Meier survival curves and Cox proportional hazards models estimated time-to-event outcomes and hazard ratios (HRs). Sensitivity analyses were performed to verify the results across varied treatment windows of 4, 8, and 10 weeks. Results: After PSM, 247,168 patients were included in the analysis for each group. The TKMS group exhibited significantly lower HRs for knee surgery (HR = 0.69, 95% CI: 0.66–0.72), opioid use (HR = 0.66, 95% CI: 0.65–0.66), and their compound events (HR = 0.66, 95% CI: 0.65–0.67) compared with the Non-TKMS group. The results remained consistent across sensitivity analyses. Conclusions: Among patients with KOA, the utilization of TKMS may significantly reduce the incidence of knee surgery and opioid use. Thus, the utilization of TKMS may be associated with a reduced need for unnecessary surgical interventions and with lower reliance on high-risk medications. Full article

Background and Objectives: To examine the prevalence of fibromyalgia syndrome (FMS) in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and its impact on treatment patterns and biologic therapy adherence. Materials and Methods: This retrospective cohort study utilized electronic health records from the Meuhedet Health Maintenance Organization in Israel between 2000 and 2020. PsO patients were matched 1:4 with controls by age, sex, and ethnicity. We assessed FMS prevalence, comorbidity burden, and treatment patterns. Cox regression and linear models evaluated the association between FMS and biologic switching and duration, adjusting for confounders. Results: Among 61,003 PsO patients and 244,012 controls, FMS prevalence was higher in PsO (3.3% vs. 2.3%, OR = 1.45, 95% CI: 1.38–1.53, p < 0.001). Among PsO patients, those with FMS were predominantly female (81.1% vs. 49.8%, p < 0.001) and had a higher prevalence of PsA (33.6% vs. 7.7%, p < 0.001). They received biologics more frequently (10.2% vs. 2.7%, p < 0.001) and were more likely to require multiple biologic lines (4.2% vs. 0.7%, p < 0.001). In PsA patients receiving biologics, FMS was associated with reduced survival on first-line therapy (6.1 vs. 10.1 years), increased switching risk (HR = 1.82, 95% CI: 1.42–2.35), and shorter treatment duration (B= −0.97 years, p = 0.001). Conclusions: In PsO patients, especially those with psoriatic arthritis, FMS is linked to greater treatment complexity and shorter biologic therapy survival, underscoring the need for tailored management strategies. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry is facilitated by transmembrane protease serine 2 (TMPRSS2), which is regulated by the androgen receptor (AR). Androgen deprivation therapy (ADT), widely used in prostate cancer treatment, may potentially modulate TMPRSS2 expression, affecting SARS-CoV-2 infection susceptibility and severity. We evaluated the impact of ADT on pulmonary TMPRSS2 expression in prostate cancer patients and analyzed differences in expression patterns associated with specific ADT regimens. We examined TMPRSS2 immunohistochemical expression in lung tissue from 20 consecutive autopsy cases of men with prostate cancer (6 receiving ADT at time of death), compared with non-ADT prostate cancer patients and age-matched women controls. Histoscores were calculated by assessing the percentage and intensity of pneumocyte TMPRSS2 expression. Prostate cancer patients receiving ADT showed significantly reduced pulmonary TMPRSS2 expression compared to non-ADT patients (mean histoscores: 152.7 vs. 225.0, p = 0.037) and age-matched women controls (mean histoscores: 152.7 vs. 238.0, p = 0.024). Direct AR antagonists (apalutamide, bicalutamide) produced greater TMPRSS2 suppression than Gonadotropin-Releasing Hormone modulators or androgen biosynthesis inhibitors. No significant correlation was observed between the TMPRSS2 expression and Gleason score, PSA levels, or underlying lung pathology. Our findings demonstrate that ADT significantly reduces pulmonary TMPRSS2 expression, with direct AR antagonists showing the strongest effect. This suggests a potential mechanistic explanation for differential COVID-19 susceptibility and provides a rationale for investigating AR-targeted therapies as potential protective interventions against SARS-CoV-2 infection severity. Full article

Background/Objectives: Gliomas are the most common tumours of the central nervous system (CNS), classified into grades I to IV based on their malignancy. Genetic and epigenetic alterations play a crucial role in glioma progression. DNA methyltransferases (DNMTs) are vital enzymes responsible for DNA methylation, with DNMT1 and DNMT3 catalysing the addition of a methyl group to the 5-carbon of cytosine in CpG dinucleotides. Targeting DNMTs with DNA methyltransferase inhibitors (DNMTi) has become a promising therapeutic approach in tumour treatment. In this study, in silico screening tools were employed to evaluate potential inhibitors of DNMT1, DNMT3A, and DNMT3B for the treatment of glioblastoma multiforme (GBM). Methods: The Gene2Drug platform was used to screen compounds and rank them based on their capacity to dysregulate DNMT genes. PRISM viability assays were performed on 68 cell lines, and DepMap data were analyzed to assess the antitumor activities of these compounds and their target genes. Candidate drug similarity was evaluated using DSEA, and compounds with p < 1 × 10⁻³ were considered statistically significant. Gene-compound interactions for DNMT1, DNMT3A, and DNMT3B were confirmed using Expression Public 24Q2, while Prism Repositioning Public data were analyzed via DepMap. Results: Glioblastoma cell lines showed sensitivity to compounds including droperidol, demeclocycline, benzthiazide, ozagrel, pizotifen, tracazolate, norcyclobenzaprine, monocrotaline, dydrogesterone, 6-benzylaminopurine, and nifedipine. SwissTargetPrediction was utilised to identify alternative molecular targets for selected compounds, revealing high-probability matches for droperidol, pizotifen, tracazolate, monocrotaline, dydrogesterone, and nifedipine. Conclusions: Integrating computational approaches with biological insights and conducting tissue-specific and experimental validations may significantly enhance the development of DNMT-targeted therapies for gliomas. Full article

Background: Monocytes can commit to different phenotypes associated with specific features required in inflammation and homeostasis. Classical and alternative activation are two extremes of monocyte polarization and are both influenced by glucocorticoids (GCs). Methods: Human monocytes were sorted from the blood of healthy individuals and activated with LPS or IL-4 and IL-13, either in the absence or presence of dexamethasone (Dex). Metabolic adjustments were analyzed using Seahorse stress tests, SCENITH, and RT-qPCR. Results: LPS enhanced glycolysis and also, to a lesser extent, oxidative phosphorylation (OXPHOS), whereas addition of Dex induced a metabolic switch in favor of the latter. In contrast, activation of monocytes with IL-4 and IL-13 exclusively stimulated OXPHOS, which was suppressed by concomitant Dex treatment. The glycolytic function of monocytes matched alterations in gene expression of glucose transporters and metabolic enzymes, which were upregulated by LPS and inhibited by Dex via interference with the mTORC1 pathway but remained unaltered in response to IL-4 and IL-13. Although the dependency of classically and alternatively activated monocytes on OXPHOS and glucose usage markedly differed, modulation by GCs was limited to the latter polarization state. Conclusions: Our findings unravel a highly selective regulation of human monocyte energy metabolism by different activating stimuli as well as by GCs. Full article

Background and Objectives: Chronic mental disorders may negatively affect sexual functioning and dyadic adjustment. This study aimed to investigate the associations between alexithymia, sexual dysfunctions, and dyadic adjustment in patients with obsessive–compulsive disorder (OCD) and to compare these variables with those of healthy controls. Materials and Methods: This case–control study included 72 patients with OCD and 82 sociodemographically matched healthy controls. All participants completed the Toronto Alexithymia Scale (TAS-20), Arizona Sexual Experiences Scale (ASEX), Yale–Brown Obsessive Compulsive Scale (YBOCS), and Dyadic Adjustment Scale (DAS). Group comparisons were conducted using independent t-tests, Mann–Whitney U tests, and chi-square tests, while correlations were examined using Pearson’s analysis. Results: Patients with OCD had significantly higher TAS-20 scores (60.97 ± 11.15 vs. 43.18 ± 8.86, p < 0.001) and ASEX total scores (18.33 ± 4.93 vs. 13.76 ± 3.55, p < 0.001), alongside lower DAS scores (total and all subscales, p < 0.001) than controls. Within the OCD group, TAS-20 scores correlated positively with the total ASEX score (r = 0.366, p = 0.002) and negatively with the total DAS score (r = −0.339, p = 0.004) and subscales (all p < 0.05). Conclusions: Patients with OCD exhibit elevated alexithymia, greater sexual dysfunction, and reduced dyadic adjustment compared with healthy controls. Furthermore, alexithymia in patients with OCD is associated with impaired sexual functioning and dyadic adjustment. Assessing alexithymic traits and addressing them in treatment may improve social and familial functioning in this population. Full article

Background: This study aimed to change the current concept of diabetic macular edema (DME) management through (1) early categorization of our DME patients into either responders or non-responders after the first intravitreal Ranibizumab (IVR) injection, and (2) finding a suitable clinical–biochemical diagnostic panel to identify the possible cause(s) of non-response in each non-responder and changing the treatment plan in each particular patient accordingly. Patients and methods: Our study included 64 eyes of 40 patients with DME (Group A, DME patients) and 40 eyes of 40 healthy individuals matched for age and sex (Group B, controls). Blood and aqueous samples were collected from the study participants before and one month after IVR injection. The DME patients were further subdivided into responders and non-responders according to their response to the first IVR injection. Lymphocyte activation markers, NETosis markers, angiogenic factors, astrocytes, innate immunity, and inflammasome markers were assessed in both groups. Results: Multivariate regression analysis revealed that macular ischemia, aqueous levels of hexokinase 1, SELL CD62L, ELANE, MPO, VEGFA, and SEMA4D were the most significant factors affecting the response to IVR (p < 0.05). Conclusions: defining our DME patients as responders and non-responders after the first IVR injection, combined with potential utilization of a clinical–biochemical panel (macular ischemia- PCR array of combined Hexokinase 1, MPO, and SEMA4D) in each non-responder, may represent a good starting point for changing the current DME management strategy. Full article

Background: Neurodegeneration is present from the earliest stages of multiple sclerosis [MS], and oxidative stress together with mitochondrial dysfunction are key contributors to neuronal injury and disease progression. Objective: To investigate the role of the antioxidant enzyme paraoxonase 1 (PON1) and serum asymmetric dimethylarginine (ADMA) levels in MS across different disease subtypes and immunomodulatory treatments. Methods: Serum lipid levels and PON1 activity were measured and compared by disease subtype and treatment in a single-center MS cohort (N = 262; CIS = 10, RRMS = 208, PPMS = 19, SPMS = 25; 110 untreated, 152 treated) and in 91 healthy controls. ADMA levels were assessed in sera from 79 MS patients (19 untreated, 60 treated) and 31 age-matched controls. Results: Median serum paraoxonase (PON) and arylesterase (ARE) activity levels were 83.8 and 127.2 IU/L in MS patients versus 85.9 and 136.9 IU/L in controls, with no significant difference for PON (p = 0.191) but a significant reduction in ARE [p = 0.003]. PON activity differed significantly among disease subtypes (p = 0.023), with the highest levels in CIS. PON and ARE activity also varied across treatment groups (p = 0.038 and p = 0.034, respectively), with longitudinal analysis indicating a measurable effect of immunomodulatory therapy on PON activity at 10 years (p = 0.0136). Significant differences in enzyme activity were observed between untreated and interferon-treated patients (PON p = 0.0055, ARE p = 0.0001), with trends toward differences in ARE under natalizumab and fingolimod. ADMA levels were lower in MS patients than controls (p < 0.0001) and differed among treatment subgroups (natalizumab, dimethyl fumarate, glatiramer acetate, untreated RRMS). Conclusions: PON1 activity and ADMA levels differ between MS subgroups and under immunomodulatory treatments. Long-term therapy was associated with increased PON1 activity, while highly effective immunomodulators reduced ADMA levels. These changes may contribute to the treatment-related reduction in disease activity and attenuation of neurodegenerative processes in MS. Full article

This work examines the effect of gadolinium (Gd) promotion on nickel-based SBA-16 catalysts for the dry reforming of methane (DRM), with the goal of improving syngas production by optimizing catalyst composition and operating conditions. Catalysts with varying Gd loadings (0.5–3 wt.%) were synthesised using co-impregnation. XRD, N₂ physisorption, FTIR, XPS, and H₂-TPR–CO₂-TPD–H₂-TPR were used to examine the structural features, textural properties, surface composition, and redox behaviour of the catalysts. XPS indicated formation of enhanced metal–support interactions, while initial and post-treatment H₂–TPR analyses showed that moderate Gd loadings (1–2 wt.%) maintained a balanced distribution of reducible Ni species. The catalysts were tested for DRM performance at 800 °C and a gas hourly space velocity (GHSV) of 42,000 mL g⁻¹ h⁻¹. 1–2 wt.% Gd-promoted catalysts achieved the highest H₂ (~67%) and CO yield (~76%). Response surface methodology (RSM) was used to identify optimal reaction conditions for maximum H₂ yield. RSM predicted 848.9 °C temperature, 31,283 mL g⁻¹ h⁻¹ GHSV, and a CH₄/CO₂ ratio of 0.61 as optimal, predicting a H₂ yield of 96.64%, which closely matched the experimental value of H₂ yield (96.66%). The 5Ni–2Gd/SBA-16 catalyst exhibited minimal coke deposition, primarily of a graphitic character, as evidenced by TGA–DSC and Raman analyses. These results demonstrate the synergy between catalyst design and process optimization in maximizing DRM efficiency. Full article

Background: Neuroimaging-based diagnostic approaches are of critical importance for the accurate diagnosis and treatment of major depressive disorder (MDD). However, multisite neuroimaging data often exhibit substantial heterogeneity in terms of scanner protocols and population characteristics. Moreover, concerns over data ownership, security, and privacy make raw MRI datasets from multiple sites inaccessible, posing significant challenges to the development of robust diagnostic models. Federated learning (FL) offers a privacy-preserving solution to facilitate collaborative model training across sites without sharing raw data. Methods: In this study, we propose the personalized Federated Gradient Matching and Contrastive Optimization (pF-GMCO) algorithm to address domain shift and support scalable MDD classification using multimodal MRI. Our method incorporates gradient matching based on cosine similarity to weight contributions from different sites adaptively, contrastive learning to promote client-specific model optimization, and multimodal compact bilinear (MCB) pooling to effectively integrate structural MRI (sMRI) and functional MRI (fMRI) features. Results and Conclusions: Evaluated on the Rest-Meta-MDD dataset with 2293 subjects from 23 sites, pF-GMCO achieved accuracy of 79.07%, demonstrating superior performance and interpretability. This work provides an effective and privacy-aware framework for multisite MDD diagnosis using federated learning. Full article

Background: The miniaturization of ureterorenoscopes increasingly enables atraumatic primary ureteroscopy, without ureteral dilation or presenting. This study aims to evaluate the feasibility and safety of primary ureteroscopy using the HU30M (6.3 Fr, HugeMed, Shenzhen HugeMed Medical Technical Development Co., Ltd., Shenzhen, China), the smallest currently available ureteroscope. Methods: We analyzed consecutive patients in whom primary ureteroscopy using the HU30M was performed or attempted, using prospectively collected in-hospital and 30-day follow-up data for retrospective evaluation. The primary outcome was the success rate of primary ostial intubation. Secondary outcomes included the stone-free rate (SFR) in patients with urolithiasis, incidence of in-hospital complications (Clavien–Dindo classification) and 30-day emergency readmission. Additionally, we conducted a propensity score-matched comparative analysis of the HU30M versus a contemporary 7.5 Fr digital single-use ureteroscope (PUSEN PU3033AH, Zhuhai Pusen Medical Technology Co., Ltd., Jinhua, China). Results: Between January and April 2025, primary ureteroscopy using the HU30M was performed or attempted in 34 patients, including four bilateral procedures. Primary ureteroscopy was defined as ureteroscopic access without prior stenting or dilation. Indications were diagnostic evaluation in 15 patients (44%), uretreroscopic stone treatment in 10 patients (29%) and endoscopic combined intrarenal surgery (ECIRS) in 9 patients (27%). Successful primary ostial intubation was achieved in 36 of 38 renal units (95%). Among urolithiasis cases, SFR was 17/19 (90%) in-hospital complications were limited to postoperative fever in two patients (6%) and no procedure-related 30-day emergency readmission occurred. In matched analyses, HU30M demonstrated significantly shorter operative times compared with the 7.5 Fr ureteroscope, while postoperative hemoglobin drop, inflammatory parameters and renal function were comparable. Conclusions: Primary ureteroscopy with HU30M is feasible and safe across diverse indications, achieving high success of atraumatic ostial access. Comparative analyses suggest procedural efficiency advantages and overall safety comparable to the current digital single-use ureteroscope standard. Full article