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The application of motor imagery in human-computer interaction and rehabilitative medicine has attracted growing attention due to recent advances in brain-computer interface technologies. However, traditional EEG decoding paradigms based on fixed frequency-band segmentation often exhibit limited performance because they fail to capture individual variability in brain rhythms. This work proposes an adaptive method that integrates the sparrow search algorithm (SSA) with Filter Bank Common Spatial Pattern (FBCSP) to optimize sub-band segmentation for motor imagery EEG decoding. SSA adaptively searches for optimal sub-band boundaries, enabling individualized frequency-band selection. Experiments on the BCI Competition IV 2a dataset under a cross-session evaluation protocol (training on session T, testing on session E) demonstrated that SSA-FBCSP effectively improves frequency-band adaptability. The SSA-FBCSP approach was further combined with Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), and k-Nearest Neighbor (KNN) classifiers to evaluate the influence of different downstream classifiers. Among them, SSA-FBCSP-LDA achieved the best performance, outperforming the conventional uniform sub-band approach by 21.76% and reaching an average accuracy of 89.92%. The adaptively selected sub-bands closely matched the ERD/ERS distribution, confirming the method's effectiveness in frequency-band optimization. Compared with recent deep-learning-based MI-EEG models, the proposed technique offers a balance of accuracy, interpretability, and computational efficiency, providing a promising direction for personalized brain-computer interface systems.

Roof-cutting and roadway retaining (RCRR) technology refers to the process of mining a coal mine face without retaining protective coal pillars. By cutting the roof, the previous section of the transportation roadway is retained as the track roadway for the next section, which has the advantages of good economic value and fast construction speed. The most important factor of RCRR effectiveness lies in the stability of the retained roadway roof, especially in areas with complex geological conditions. Due to high ground stress, ground water pressure and weak surrounding rock, the roof stabilizing and bearing mechanism is complex, restricting the promotion of RCRR. In response to above difficulties, the fiber reinforced polymer (FRP) anchoring cable is introduced for the roof stability control owing to its high strength and low costs. In this paper, the calculation formula of the bearing strength of the Fiber reinforced polymer anchoring cable in the top cutting and retaining roadway is derived. We have also discussed the effects of various strength properties of the FRP anchoring cable, including cohesion, internal friction angle, and preload, as well as layout parameters such as cable spacing, length, and diameter. The results indicate that as the strength parameters, preload, length, and diameter of FRP anchoring cable increase, so does the bearing strength of the FRP anchoring cable in the roadway. Therefore, using high-strength and high preload FRP anchoring cables with grouting reinforcement can effectively ensure the stability of the retained roadway roof. The research results can provide theoretical and practical experience for relevant engineering cases.

Neurofibromatosis type 1 (NF1) plexiform neurofibromas (PNs) are progressive, multicellular neoplasms that cause morbidity and may transform to sarcoma. Treatment of Nf1 fl/fl ; Postn -Cre mice with cabozantinib, an inhibitor of multiple tyrosine kinases, caused a reduction in PN size and number and differential modulation of kinases in cell lineages that drive PN growth. Based on these findings, the Neurofibromatosis Clinical Trials Consortium conducted a phase II, open-label, nonrandomized Simon two-stage study to assess the safety, efficacy and biologic activity of cabozantinib in patients ≥16 years of age with NF1 and progressive or symptomatic, inoperable PN ( NCT02101736 ). The trial met its primary outcome, defined as ≥25% of patients achieving a partial response (PR, defined as ≥20% reduction in target lesion volume as assessed by magnetic resonance imaging (MRI)) after 12 cycles of therapy. Secondary outcomes included adverse events (AEs), patient-reported outcomes (PROs) assessing pain and quality of life (QOL), pharmacokinetics (PK) and the levels of circulating endothelial cells and cytokines. Eight of 19 evaluable (42%) trial participants achieved a PR. The median change in tumor volume was 15.2% (range, +2.2% to −36.9%), and no patients had disease progression while on treatment. Nine patients required dose reduction or discontinuation of therapy due to AEs; common AEs included gastrointestinal toxicity, hypothyroidism, fatigue and palmar plantar erythrodysesthesia. A total of 11 grade 3 AEs occurred in eight patients. Patients with PR had a significant reduction in tumor pain intensity and pain interference in daily life but no change in global QOL scores. These data indicate that cabozantinib is active in NF1-associated PN, resulting in tumor volume reduction and pain improvement. Cabozantinib, an inhibitor of multiple receptor tyrosine kinases, has efficacy in a mouse model of neurofibromatosis type I and has clinical activity in reducing plexiform neurofibroma volume in a phase II trial of patients with NF1.

Background Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that has been found to be associated with dysregulation of gastrointestinal functions and gut microbial homeostasis (the so-called “gut-brain axis”). ASD is often accompanied by poor performances in social interaction and repetitive behaviors. Studies on the gut-brain axis provide novel insights and candidate targets for ASD therapeutics and diagnosis. Based on the ASD mice model, this work aims to reveal the mechanisms behind the interaction of intestinal barrier function and probiotics in ASD mouse models. Results We found an altered intestinal barrier in both BTBR T + Itpr3 tf /J ( BTBR) and valproic acid (VPA) mice, including increased intestinal permeability, decreased expression of intestinal tight junction proteins (claudin1, claudin3, and occludin), and increased levels of IL-6, TNF-α, and IFN-γ. Based on intestinal microbial alternation, C. butyricum can drive reduced expression of histone deacetylases 1 (HDAC1) and enhanced intestinal barrier function, significantly promoting behavioral abnormalities of ASD in BTBR mice. In parallel, we confirmed that C. butyricum was involved in the regulation of intestinal function by the Trek1 channel, indicating that it is a target of C . butyricum /butyric acid to improve intestinal barrier function in ASD mice. Conclusions Our finding provides solid evidence for the gut microbiota involved in ASD through the brain-gut axis. In addition, the probiotics C . butyricum hold promise to improve gut health and ameliorate behavioral abnormalities associated with ASD.

The extracellular signal-regulated kinases (ERK1 and 2) are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/-) bone marrow mononuclear cells (BMMNCs) demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/-) BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

Introduction We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60 years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. Methods This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission < 30 days) and compared severity between RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. Results We included 706 RSV patients (635 inpatients and 71 outpatients), and 598 influenza and 60 COVID-19 hospitalized controls with comparable sociodemographic profile. Among RSV patients, 96 (15%) had a subtype identified: 56% A, 42% B, and 2% A + B. Eighty-one percent of RSV patients had cardiovascular conditions, 65% endocrine/metabolic, 46% chronic lung, and 43% immunocompromising conditions. Thirty-six percent were coinfected (vs. 21% influenza and 20% COVID-19; p  =  < .0001 and 0.01). Ninety-two percent had signs of lower respiratory infection (vs. 85% influenza and 72% COVID-19, p  =  < .0001) and 27% cardiovascular signs (vs. 20% influenza and 8% COVID-19, p  = 0.0031 and 0.0009). Laboratory parameters of anemia, inflammation, and hypoxemia were highest in RSV. Among RSV, being a previous smoker (adjusted OR 2.81 [95% CI 1.01, 7.82]), coinfection (4.34 [2.02, 9.34]), and having cardiovascular (3.79 [2.17, 6.62]), neurologic (2.20 [1.09, 4.46]), or chronic lung (1.93 [1.11, 3.38]) diseases were risks for hospitalization. Being resident in care institutions (1.68 [1.09, 2.61]) or having a coinfection (1.91[1.36, 2.69]) were risks for higher severity, while RSV subtype was not associated with severity. Whereas RSV and influenza patients did not show differences in severity, RSV patients had 68% (38–84%) lower odds of experiencing any severe outcome compared to COVID-19. Conclusions RSV especially affects those with comorbidities, coinfections, and living in care institutions. RSV vaccination could have an important public health impact in this population.

Introduction We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. Methods We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. Results We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 ( p  = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19. Conclusions RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6–24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding.

Schwannomas are tumors of the Schwann cells that cause chronic pain, numbness, and potentially life-threatening impairment of vital organs. Despite the identification of causative genes, including NF2 (Merlin), INI1/SMARCB1, and LZTR1, the exact molecular mechanism of schwannoma development is still poorly understood. Several studies have identified Merlin as a key regulator of the Hippo, MAPK, and PI3K signaling pathways; however, definitive evidence demonstrating the importance of these pathways in schwannoma pathogenesis is absent. Here, we provide direct genetic evidence that dysregulation of the Hippo pathway in the Schwann cell lineage causes development of multiple schwannomas in mice. We found that canonical Hippo signaling through the effectors YAP/TAZ is required for schwannomagenesis and that MAPK signaling modifies schwannoma formation. Furthermore, cotargeting YAP/TAZ transcriptional activity and MAPK signaling demonstrated a synergistic therapeutic effect on schwannomas. Our new model provides a tractable platform to dissect the molecular mechanisms underpinning schwannoma formation and the role of combinatorial targeted therapy in schwannoma treatment.

Skeletal abnormalities including osteoporosis and osteopenia occur frequently in both pediatric and adult neurofibromatosis type 1 (NF1) patients. NF1 (Nf1) haploinsufficient osteoclasts and osteoclast progenitors derived from both NF1 patients and Nf1(+/-) mice exhibit increased differentiation, migration, and bone resorptive capacity in vitro, mediated by hyperactivation of p21(Ras) in response to limiting concentrations of macrophage-colony stimulating factor (M-CSF). Here, we show that M-CSF binding to its receptor, c-Fms, results in increased c-Fms activation in Nf1(+/) (-) osteoclast progenitors, mediating multiple gain-in-functions through the downstream effectors Erk1/2 and p90RSK. PLX3397, a potent and selective c-Fms inhibitor, attenuated M-CSF mediated Nf1(+/-) osteoclast migration by 50%, adhesion by 70%, and pit formation by 60%. In vivo, we administered PLX3397 to Nf1(+/-) osteoporotic mice induced by ovariectomy (OVX) and evaluated changes in bone mass and skeletal architecture. We found that PLX3397 prevented bone loss in Nf1(+/-)-OVX mice by reducing osteoclast differentiation and bone resorptive activity in vivo. Collectively, these results implicate the M-CSF/c-Fms signaling axis as a critical pathway underlying the aberrant functioning of Nf1 haploinsufficient osteoclasts and may provide a potential therapeutic target for treating NF1 associated osteoporosis and osteopenia.

Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a complex genetic disorder with a high predisposition of numerous skeletal dysplasias including short stature, osteoporosis, kyphoscoliosis, and fracture non-union (pseudoarthrosis). We have developed murine models that phenocopy many of the skeletal dysplasias observed in NF1 patients, including reduced bone mass and fracture non-union. We also show that the development of these skeletal manifestations requires an Nf1 haploinsufficient background in addition to nullizygous loss of Nf1 in mesenchymal stem/progenitor cells (MSCs) and/or their progenies. This is replicated in two animal models of NF1, PeriCre(+);Nf1(flox/-) and Col2.3Cre(+);Nf1(flox/-) mice. Adoptive transfer experiments demonstrate a critical role of the Nf1+/- marrow microenvironment in the impaired fracture healing in both models and adoptive transfer of WT bone marrow cells improves fracture healing in these mice. To our knowledge, this is the first demonstration of a non-cell autonomous mechanism in non-malignant NF1 manifestations. Collectively, these data provide evidence of a combinatory effect between nullizygous loss of Nf1 in osteoblast progenitors and haploinsufficiency in hematopoietic cells in the development of non-malignant NF1 manifestations.