Search Results (761)

Background/Objectives: Male infertility is a major health concern with a complex etiopathology, yet a substantial proportion of cases remain idiopathic. Mitochondrial dysfunction and non-coding RNA (ncRNA) deregulation have both been implicated in impaired spermatogenesis, but their interplay remains poorly understood. This study aimed to identify infertility-specific variants in ncRNAs that affect mitochondrial dynamics and homeostasis and to explore their roles. Methods: Whole-genome sequencing (WGS) was performed on genomic DNA samples from teratozoospermic, asthenozoospermic, oligozoospermic, and normozoospermic men. Variants uniquely present in infertile individuals and mapped to ncRNAs that affect mitochondrial dynamics were selected and prioritized using bioinformatics tools. An independent transcriptomic validation was conducted using RNA-sequencing data from testicular biopsies of men with non-obstructive azoospermia (NOA) to determine whether the ncRNAs harboring WGS-derived variants were transcriptionally altered. Results: We identified several infertility-specific variants located in lncRNAs known to interact with mitochondrial regulators, including GAS5, HOTAIR, PVT1, MEG3, and CDKN2B-AS1. Transcriptomic analysis confirmed significant deregulation of these lncRNAs in azoospermic testicular samples. Bioinformatic analysis also implicated the disruption of lncRNA–miRNA–mitochondria networks, potentially contributing to mitochondrial membrane potential loss, elevated reactive oxygen species (ROS) production, impaired mitophagy, and germ cell apoptosis. Conclusions: Our integrative genomic and transcriptomic analysis highlights lncRNA–mitochondrial gene interactions as a novel regulatory layer in male infertility, while the identified lncRNAs hold promise as biomarkers and therapeutic targets. However, future functional studies are warranted to elucidate their mechanistic roles and potential for clinical translation in reproductive medicine. Full article

Background/Objectives: Nowadays, intravascular lithotripsy (IVL) has emerged as a novel technique for treatment of vascular calcifications, first in coronary and then in peripheral arteries. In the current literature there is little evidence that describes IVL as an effective and safe solution in treating severe aortic and aorto-iliac calcifications. The aim of this study is to report current available data about the use of IVL in treating aortic and aorto-iliac calcified lesions and its application in facilitating other endovascular procedures. Methods: the present review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines. Preliminary searches were conducted on MEDLINE and Pubmed from January 2015 to February 2025. Studies were divided into 3 main categories depending on the location of calcifications and the type of treatment: IVL in visceral and infrarenal obstructive disease (group 1), IVL in aorto-iliac obstructive disease (group 2), IVL used to facilitate other endovascular procedures. Main primary outcomes in the perioperative period were technical and clinical successes and perioperative complications. Primary outcomes at 30 days and mid-term (2 years) were overall survival, limb salvage rate, primary patency, primary assisted patency, secondary patency, and residual stenosis. Results: Sixteen studies were identified for a total of 1674 patients. Technical and clinical successes were 100%, with low rates of perioperative complications. Dissection rate reaches up to 16.1% in some studies, without any differences compared to plain old balloon angioplasty (POBA) alone (22.8%; p = 0.47). At 30 days, limb salvage and survival rates were 100%. At 2 years, primary patency, assisted primary patency, and secondary patency were 95%, 98%, and 100%, respectively, with no difference compared to IVL + stenting. Conclusions: IVL has emerged as a novel approach to treat severe calcified lesions in visceral and aorto-iliac atherosclerotic disease and to facilitate other endovascular procedures. This technique seems to offer satisfactory early and mid-term outcomes in terms of primary, primary assisted patency, and secondary patency with low complication rates. Full article

This study aims to characterize short-wave infrared (SWIR) reflectance spectra at cranial (at the scalp overlying the frontal cortex and the temporal bone window) and extracranial (biceps and triceps) sites in patients with multiple sclerosis (MS) and age-/sex-matched controls. We sought to identify the diagnostic accuracy of wavelength-specific patterns in distinguishing MS from normal controls and spectral markers associated with disability (e.g., Expanded Disability Status Scale scores). To achieve these objectives, we employed a multi-site SWIR spectroscopy acquisition protocol that included measurements from traditional cranial locations as well as extracranial reference sites. Advanced spectral analysis techniques, including wavelength-dependent absorption modeling and machine learning-based classification, were applied to differentiate MS-related hemodynamic changes from normal physiological variability. Classification models achieved perfect performance (accuracy = 1.00), and cortical site regression models showed strong predictive power (EDSS: R²_CV = 0.980; FSS: R²_CV = 0.939). Variable Importance in Projection (VIP) analysis highlighted key wavelengths as potential spectral biomarkers. This approach allowed us to explore novel biomarkers of neural and systemic impairment in MS, paving the way for potential clinical applications of SWIR spectroscopy in disease monitoring and management. In conclusion, spectral analysis revealed distinct wavelength-specific patterns collected from cranial and extracranial sites reflecting biochemical and structural differences between patients with MS and normal subjects. These differences are driven by underlying physiological changes, including myelin integrity, neuronal density, oxidative stress, and water content fluctuations in the brain or muscles. This study shows that portable spectral devices may contribute to bedside individuation and monitoring of neural diseases, offering a cost-effective alternative to repeated imaging. Full article

Background and Objectives: Acute metastatic cord compression (AMSCC) and femoral impending/pathological fracture negatively impact a patient’s quality of life, morbidity and survival, and are considered significant life events. This study aims to compare AMSCC and FMD as distinct yet overlapping metastatic orthopedic emergencies, addressing whether they represent sequential disease stages or distinct patient subpopulations—an analysis critical for prognosis and treatment planning. Materials and Methods: Records of all patients who underwent surgery for a femoral metastatic disease (FMD) over a decade (2004–2015) and patients who were treated for acute metastatic spinal compression (AMSCC) (2007–2017) were retrieved. There were no patients lost to follow-up. Results: The treatment cohorts were similar in terms of age, gender, tumour origin, and the number of spinal metastases. Fifty-four patients were diagnosed with AMSCC. Following treatment, the Frankel muscle grading improved by 0.5 ± 0.8 grades. Two hundred and eighteen patients underwent surgical intervention for FMD. Seventy percent of femoral metastases were located in the femoral neck and trochanteric area. Impending fractures accounted for 52% of the cohort. The FMD cohort, including impending and pathological fractures, was similar to the AMSCC cohort in terms of age and the time interval between cancer diagnosis and surgery (56.7 ± 74.2 vs. 51.6 ± 69.6, respectively, p = 0.646). The Karnofsky functional score was higher for the FMD cohort (63.3 ± 16.2) than for the AMSCC cohort (48.5 ± 19.5; p < 0.001). The mean survival time for the FMD cohort was double that of the AMSCC, at 18.4 ± 23.5 months versus 9.1 ± 13.6 months, respectively (p = 0.006). Conclusions: In conclusion, this study is novel in proposing that FMD and AMSCC are distinct clinical entities, differing in their impact on patient function and, most importantly, on patient survival. Full article

Robotic search of people in human-centered environments, including healthcare settings, is challenging, as autonomous robots need to locate people without complete or any prior knowledge of their schedules, plans, or locations. Furthermore, robots need to be able to adapt to real-time events that can influence a person’s plan in an environment. In this paper, we present MLLM-Search, a novel zero-shot person search architecture that leverages multimodal large language models (MLLM) to address the mobile robot problem of searching for a person under event-driven scenarios with varying user schedules. Our approach introduces a novel visual prompting method to provide robots with spatial understanding of the environment by generating a spatially grounded waypoint map, representing navigable waypoints using a topological graph and regions by semantic labels. This is incorporated into an MLLM with a region planner that selects the next search region based on the semantic relevance to the search scenario and a waypoint planner that generates a search path by considering the semantically relevant objects and the local spatial context through our unique spatial chain-of-thought prompting approach. Extensive 3D photorealistic experiments were conducted to validate the performance of MLLM-Search in searching for a person with a changing schedule in different environments. An ablation study was also conducted to validate the main design choices of MLLM-Search. Furthermore, a comparison study with state-of-the-art search methods demonstrated that MLLM-Search outperforms existing methods with respect to search efficiency. Real-world experiments with a mobile robot in a multi-room floor of a building showed that MLLM-Search was able to generalize to new and unseen environments. Full article

Background: Hemiplegic migraine (HM) is a rare and severe subtype of migraine with a complex genetic basis. Although pathogenic variants in CACNA1A, ATP1A2, and SCN1A explain some familial cases, a significant proportion of patients remain genetically undiagnosed. Increasing evidence points to an overlap between migraine and cerebral small vessel disease (SVD), implicating vascular dysfunction in HM pathophysiology. Objective: This study aimed to identify rare or novel variants in genes associated with SVD in a cohort of patients clinically diagnosed with HM who tested negative for known familial hemiplegic migraine (FHM) pathogenic variants. Methods: We conducted a case-control association analysis of whole exome sequencing (WES) data from 184 unrelated HM patients. A targeted panel of 34 SVD-related genes was assessed. Variants were prioritised based on rarity (MAF ≤ 0.05), location (exonic/splice site), and predicted pathogenicity using in silico tools. Statistical comparisons to gnomAD’s Non-Finnish European population were made using chi-square tests. Results: Significant variants were identified in several SVD-related genes, including LRP1 (p.Thr4077Arg), COL4A1 (p.Pro54Leu), COL4A2 (p.Glu1123Gly), and TGFBR2 (p.Met148Leu and p.Ala51Pro). The LRP1 variant showed the strongest association (p < 0.001). All key variants demonstrated pathogenicity predictions in multiple computational models, implicating them in vascular dysfunction relevant to migraine mechanisms. Conclusions: This study provides new insights into the genetic architecture of hemiplegic migraine, identifying rare and potentially deleterious variants in SVD-related genes. These findings support the hypothesis that vascular and cellular maintenance pathways contribute to migraine susceptibility and may offer new targets for diagnosis and therapy. Full article

Background/Objectives: Violence is a significant occupational health issue for paramedics, yet underreporting limits efforts to identify and mitigate risk. Leveraging a novel, point-of-event violence reporting system, we aimed to identify characteristics of 9-1-1 calls associated with an increased risk of violence in a single paramedic service in Ontario, Canada. Methods: We retrospectively analyzed all electronic violence and patient care reports filed by paramedics in Peel Region and used logistic regression to identify call-level predictors of any violence and, more specifically, physical or sexual assault. Results: In total, 374 paramedics filed 974 violence reports, 40% of which documented an assault, corresponding to a rate of 4.18 violent encounters per 1000 9-1-1 calls. In adjusted models, the risk of violence was elevated for calls originating from non-residential locations (e.g., streets, hotels, bars), occurring during afternoon or overnight shifts, and involving young or working-age males. Presenting problems related to intoxication, mental health, or altered mental status were strongly associated with increased risk, with particularly high adjusted odds ratios for assault. Conclusions: These findings support the utility of near-miss and violence surveillance systems and highlight the need for multidisciplinary crisis response to high-risk calls, especially those involving mental health or substance use. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

Aiming for convenience and the low cost of goods transfer between towns, this paper proposes a trade hub location and allocation method based on a novel artificial eagle-inspired optimization algorithm. Firstly, the trade hub location and allocation model is established, taking the total cost consisting of construction and transportation costs as the objective function. Then, to solve the nonlinear model, a novel artificial eagle optimization algorithm (AEOA) is proposed by simulating the collective migration behaviors of artificial eagles when facing a severe living environment. Three main strategies are designed to help the algorithm effectively explore the decision space: the situational awareness and analysis stage, the free exploration stage, and the flight formation integration stage. In the first stage, artificial eagles are endowed with intelligent thinking, thus generating new positions closer to the optimum by perceiving the current situation and updating their positions. In the free exploration stage, artificial eagles update their positions by drawing on the current optimal position, ensuring more suitable habitats can be found. Meanwhile, inspired by the consciousness of teamwork, a formation flying method based on distance information is introduced in the last stage to improve stability and success rate. Test results from the CEC2022 suite indicate that the AEOA can obtain better solutions for 11 functions out of all 12 functions compared with 8 other popular algorithms. Faster convergence speed and stronger stability of the AEOA are also proved by quantitative analysis. Finally, the trade hub location and allocation method is proposed by combining the optimization model and the AEOA. By solving two typical simulated cases, this method can select suitable hubs with lower construction costs and achieve reasonable allocation between hubs and the rest of the towns to reduce transportation costs. Thus, it is used to solve the trade hub location and allocation problem of Henan province in China to help the government make sound decisions. Full article

Background/Objectives: Cardiovascular diseases are a global health issue with an increasing burden and are exacerbated by hypertension. High blood pressure is partly attributed to genetic variants that are generally not well understood or extensively studied in sub-Saharan African populations. Variants linked to blood pressure have been found through genome-wide association studies (GWASs), which were mostly conducted among European ancestry populations; however, limited research has been undertaken in Africa. The current study evaluated single-nucleotide polymorphisms (SNPs) of PCSK9, ABCA1, LPL, and PON1 in relation to blood pressure measurements of 1839 Ghanaian adults. Methods: Genotypes were extracted from data generated by the H3Africa SNP array. After adjusting for sex, age, smoking, and body mass index (BMI), inferential statistics were used to investigate the relationships between SNPs and blood pressure (BP) indices. Additionally, Bonferroni correction was used to adjust for multiple testing. Results: Diastolic blood pressure (DBP) and the minor allele T of the PCSK9 variant (rs17111557) were positively associated at p = 0.006 after covariate adjustments. Although this novel DBP-associated variant is located in the 3′ untranslated region (3′ UTR) of the PCSK9 gene, in silico functional prediction suggests it is an expression quantitative trait locus (eQTL) that may change the binding site of transcription factors, potentially altering the rate of transcription and impacting DBP in this Ghanaian population. Conclusions: Our findings highlight the role of genetics in hypertension risk and the potential of discovering new therapies targeting isolated diastolic blood pressure in this rural African population. Full article

Background/Objectives: Developmental dysplasia of the hip (DDH) affects 1–3% of newborns and requires early detection for optimal outcomes. DDH involves abnormal acetabular–femoral congruence between the acetabulum and femoral head, resulting from either shallow acetabular development or delayed femoral ossification of the femoral head. We evaluated the ossification nucleus of the femoral head (ONFH) to determine prevalence, radiographic timing, and associations with perinatal factors. Methods: We analyzed 100 pelvic radiographs of infants between 90 and 150 days of age. Participants were selected by convenience sampling, based on inclusion criteria. We identified the presence of ONFH and measured biometric parameters, morphology, and anatomical location. Sociodemographic and perinatal data were collected from the participating infants. Results: The prevalence of ONFH was 33%, and the mean age at visualization was 104 days. The presence of ONFH was correlated with birth weight (p = 0.011), discharge weight (p = 0.005), and weight at 1 month (p = 0.034). In our study, female sex (p = 0.004) was associated with a 4.966-fold higher odds of ONFH prevalence compared to males. Conclusions: This study provides relevant evidence regarding the prevalence, morphology, and characteristics of ONFH. Few studies report this information on ONFH in different populations. The optimal timing for radiographic visualization of ONFH in infants remains undefined, but the appearance of the ONFH was concentrated around 104 days of life. The novel association between weight and ONFH provides new insights into DDH. This provides new insights for DDH screening. This association warrants further research for the early detection of DDH. Full article

Temporal lobe epilepsy (TLE) is a common drug-resistant form of epilepsy, often accompanied by cognitive and emotional disturbances, highlighting the urgent need for novel therapies. Scorpion Venom Heat-Resistant Synthetic Peptide (SVHRSP), isolated and synthetically derived from scorpion venom, has shown anti-epileptic and neuroprotective potential. This study evaluated the anti-epileptic effects of SVHRSP in a kainic acid (KA)-induced TLE rat model. Our results demonstrated that SVHRSP (0.81 mg/kg/day) reduced the frequency and severity of spontaneous seizures. Behavioral tests showed improved cognitive performance in the novel object recognition, object location, and T-maze tasks, as well as reduced anxiety-like behavior in the open-field test. Moreover, SVHRSP mitigated hippocampal neuronal loss and glial activation. Transcriptomic analysis indicated that SVHRSP upregulates genes involved in adhesion molecule-triggered and axon guidance pathways. Western blotting and immunofluorescence further confirmed that SVHRSP restored dendritic (MAP2), axonal (NFL), and synaptic (PSD95) marker expression, elevated the functionally important L1CAM fragment (L1-70), and increased myelin basic protein-induced serine protease activity responsible for L1-70 generation. Blockade of L1CAM expression diminished the neuroprotective effects of SVHRSP, suggesting a critical role for L1CAM-mediated synapse functions. This study is the first to reveal the therapeutic potential of SVHRSP in TLE via L1CAM-associated mechanisms. Full article

Background/Objectives: Cell–cell communication (CCC) is a critical process within the tumor microenvironment, governing regulatory interactions between cancer cells and other cellular subpopulations. Aiming to improve the accuracy and completeness of intercellular gene-regulatory network inference, we constructed a novel spatial-resolved gene-regulatory network framework (spGRN). Methods: Firstly, the spatial multi-omics data of colorectal cancer (CRC) patients were analyzed. We precisely located the tumor boundaries and then systematically constructed the spGRN framework to study the network regulation. Subsequently, the key signaling molecules obtained by the spGRN were identified and further validated by the spatial-proteomics dataset. Results: Through the constructed spatial gene regulatory network, we found that in the communication with malignant cells, the highly expressed ligands LIF and LGALS3BP and receptors IL6ST and ITGB1 in fibroblasts can promote tumor proliferation, and the highly expressed ligands S100A8/S100A9 in plasma cells play an important role in regulating inflammatory responses. Further, validation of the key signaling molecules by the spatial-proteomics dataset highlighted the role of these genes in mediating the regulation of boundary-related cells. Furthermore, we applied the spGRN to publicly available single-cell and spatial-transcriptomics datasets from three other cancer types. The results demonstrate that ITGB1 and its target genes FOS/JUN were commonly expressed in all four cancer types, indicating their potential as pan-cancer therapeutic targets. Conclusion: the spGRN was proven to be a useful tool to select signal molecules as potential biomarkers or valuable therapeutic targets. Full article

Recent advancements in the detection Transformer model have demonstrated remarkable accuracy in real-time object detection using an end-to-end approach. DETR leverages the concept of object queries, which act as “questions” to determine the presence and location of objects. However, the excessive number of object queries significantly increases computational complexity, leading to higher training and inference times, greater memory consumption, and increased costs. To address this issue, this paper introduces the selected query detection Transformer, a novel approach that optimizes the selection of object queries in the decoder. By progressively filtering and reducing unnecessary queries, the selected query detection Transformer maintains model performance while significantly reducing computational overhead, resulting in faster training and inference times. Full article

The assembly optimization design of satellite components is a crucial element in the overall design of satellites. In this paper, a novel three-dimensional assembly optimization design problem (3D-AODP) for multi-module micro–nano satellite components is proposed according to the engineering requirements, aiming at optimizing the satellite mass characteristics, and taking into account constraints such as space interference, space occupation and special location. Multi-module micro–nano satellites are a new type of satellite configuration based on the assembly of multiple U-shaped cube units. The 3D-AODP of its components is a challenging two-layer composite optimization task involving discrete variable optimization of component allocation and continuous variable optimization of component layout, which interact with each other. To solve the problem, a hybrid assembly optimization method based on tabu search (TS) and multi-objective differential evolutionary (MODE) algorithms is proposed, in which the assignment problem of the components is converted into a domain search problem by the TS algorithm. The space interference constraints and space occupancy constraints of the components are considered, and an assignment scheme with the minimum mass difference is obtained. On this basis, a bi-objective differential evolutionary algorithm is used to develop the layout optimization problem for the components, which takes into account the spatial non-interference constraints and special location constraints of the components, and obtains the Pareto solution set of the assembly scheme under the optimal mass characteristics (moment of inertia and product of inertia). Finally, the feasibility and effectiveness of the proposed method is demonstrated by an engineering case. Full article