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Anterior shoulder instability with glenoid bone lesion can be treated with the Eden-Hybinette procedure utilizing a tricortical iliac crest bone graft or the Latarjet procedure. This study aimed to evaluate the glenohumeral joint (GHJ) kinematics throughout an external shoulder rotation following the Eden-Hybinette and Latarjet procedures. Nine human specimens were examined with dynamic radiostereometry during a GHJ external rotation with anteriorly directed loads from 0 to 30 N. In 30- and 60-degree GHJ abduction, the kinematics (measured as the humeral head center and contact point) was sequentially recorded for a 15% anterior glenoid bone lesion, the Eden-Hybinette, and the Latarjet procedure. The Latarjet and Eden-Hybinette procedures resulted in up to 9.7 mm (95%CI 0.5; 18.8) more posterior and a 7.4 mm (95%CI 0.3; 14.4) superior humeral head center location compared to the glenoid bone lesion. With 0-20 N anterior directed loads, the Latarjet procedure resulted in a more posterior humeral head center and contact point of up to 7.6 mm (95%CI 3.6; 11.5), especially in 60 degrees of GHJ abduction, compared to the Eden-Hybinette procedure. Opposite, at 30 N anterior-directed load, the Eden-Hybinette procedure resulted in a more posterior humeral head center of up to 7.6 mm (95%CI 0.3; 14.9) in 30 degrees GHJ abduction compared to the Latarjet procedure. The results support considering the Latarjet procedures in patients who need the stabilizing effect with the arm in the abducted and externally rotated position (e.g., throwers) and the Eden-Hybinette procedure in patients exposed to high anterior-directed loads with the arm at lower abduction angles (e.g., epilepsia)., (© 2024 Orthopaedic Research Society.)

Poor outcome following traumatic acute subdural hematoma (ASDH) is associated with the severity of the primary injury and secondary injury including cerebral edema and ischemia. However, the underlying secondary injury mechanism contributing to elevated intracranial pressure (ICP) and high mortality rate remains unclear. Cerebral edema occurs in response to the exposure of the intracellular fixed charge density (FCD) after cell death, causing ICP to increase. The increased ICP from swollen tissue compresses blood vessels in adjacent tissue, restricting blood flow and leading to ischemic damage. We hypothesize that the mass occupying effect of ASDH exacerbates the ischemic injury, leading to ICP elevation, which is an indicator of high mortality rate in the clinic. Using FEBio (febio.org) and triphasic swelling biomechanics, this study modeled clinically relevant ASDHs and simulated post-traumatic brain swelling and ischemia to predict ICP. Results showed that common convexity ASDH significantly increased ICP by exacerbating ischemic injury, and surgical removal of the convexity ASDH may control ICP by preventing ischemia progression. However, in cases where the primary injury is very severe, surgical intervention alone may not effectively decrease ICP, as the contribution of the hematoma to the elevated ICP is insignificant. In addition, interhemispheric ASDH, located between the cerebral hemispheres, does not significantly exacerbate ischemia, supporting the conservative surgical management generally recommended for interhemispheric ASDH. The joint effect of the mass occupying effect of the blood clot and resulting ischemia contributes to elevated ICP which may increase mortality. Our novel approach may improve the fidelity of predicting patient outcome after motor vehicle crashes and traumatic brain injuries due to other causes., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

With dental implant treatment becoming the gold standard, the need for effective bone augmentation prior to implantation has grown. This study aims to evaluate a bone augmentation strategy integrating three key growth factors: bone morphogenetic protein-2 (BMP-2), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Collagen scaffolds incorporating BMP-2, IGF-1, or VEGF were fabricated and categorized into five groups based on their content: scaffold alone; BMP-2 alone (BMP-2); BMP-2 and IGF-1 (BI); BMP-2, IGF-1, and VEGF (BIV); and BMP-2 and IGF-1 with an earlier release of VEGF (BI + V). The prepared scaffolds were surgically implanted into the calvarias of C57BL/6JJcl mice, and hard tissue formation was assessed after 10 and 28 days through histological, tomographic, and biochemical analyses. The combination of BMP-2 and IGF-1 induced a greater volume of hard tissue augmentation compared with that of BMP-2 alone, regardless of VEGF supplementation, and these groups had increased levels of cartilage compared with others. The volume of hard tissue formation was greatest in the BIV group. In contrast, the BI + V group exhibited a hard tissue volume similar to that of the BI group. While VEGF and CD31 levels were highest in the BIV group at 10 days, there was no correlation at the same time point between hard tissue formation and the quantity of M2 macrophages. In conclusion, the simultaneous release of BMP-2, IGF-1, and VEGF proved to be effective in promoting bone augmentation., (© 2024 Wiley Periodicals LLC.)

Background: Ferroptosis, a recently discovered iron-dependent cell death, is linked to various diseases but its role in endometriosis is still not fully understood. Methods: In this study, we integrated microarray data of endometriosis from the GEO database and ferroptosis-related genes (FRGs) from the FerrDb database to further investigate the regulation of ferroptosis in endometriosis and its impact on the immune microenvironment. WGCNA identified ferroptosis-related modules, annotated by GO & KEGG. MNC algorithm pinpointed hub FRGs. Cytoscape construct a ceRNA network, and ROC curves evaluated diagnostic efficacy of hub FRGs. Consensus cluster analysis identified ferroptosis subclusters, and CIBERSORT assessed immune infiltration of these subclusters. Finally, RT-qPCR validated hub FRG expression in clinical tissues. Results: We identified two ferroptosis modules of endometriosis, and by enrichment analysis, they are closely linked with autophagy, mTOR, oxidative stress, and FOXO pathways. Furthermore, we identified 10 hub FRGs, and the ROC curve showed better predictive ability for diagnosing. RT-qPCR confirmed that the tissue expression of 10 hub FRGs was mostly consistent with the database results. Subsequently, we developed a ceRNA network based on 4 FRGs (BECN1, OSBPL9, TGFBR1, GSK3B). Next, we identified two ferroptosis subclusters of endometriosis and discovered that they are closely linked with endometriosis stage. Importantly, immune enrichment analysis illustrated that the expression levels of immune cells and immune checkpoint genes were significantly different in the two ferroptosis subclusters. Specifically, the ferroptosis subcluster with stage III-IV of endometriosis is more inclined to the immunosuppressive microenvironment. Conclusions: Our study showed that ferroptosis may jointly promote endometriosis progression by remodeling the immune microenvironment, offering new insights into pathogenesis and therapeutics. [ABSTRACT FROM AUTHOR]

Light provides the necessary energy for plant photosynthesis, which allows plants to produce organic matter and energy conversion, during plant growth and development. Light provides material energy to plants as the basis for cell division and differentiation, chlorophyll synthesis, tissue growth and stomatal movement, and light intensity, photoperiod, and light quality play important roles in these processes. There are several regulatory mechanisms involved in sugar metabolism in plants, and light, as one of the regulatory factors, affects cell wall composition, starch granules, sucrose synthesis, and vascular bundle formation. Similarly, sugar species and genes are affected in the context of light-regulated sugar metabolism. We searched the available databases and found that there are fewer relevant reviews. Therefore, this paper provides a summary of the effects of light on plant growth and development and sugar metabolism, further elaborates on the mechanisms of light effects on plants, and provides some new insights for a better understanding of how plant growth is regulated under different light conditions. [ABSTRACT FROM AUTHOR]

Background/objectives: Mycosis fungoides (MF) is a rare malignancy, with an indolent course in the early stages of the disease. However, due to major molecular and clinical heterogeneity, patients at an advanced stage of the disease have variable responses to treatment and considerably reduced life expectancy. Today, there is a lack of specific markers for the progression from early to advanced stages of the disease. To address these challenges, the non-interventional BIO-MUSE trial was initiated. Here, we report on a case study involving one patient, where combined omics analysis of tissue and blood was used to reveal the unique molecular features associated with the progression of the disease. Methods: We applied 10× genomics-based single-cell RNA sequencing to CD3+ peripheral T-cells, combined with T-cell receptor sequencing, to samples collected at multiple timepoints during the progression of the disease. In addition, GeoMx-based digital spatial profiling of T-helper (CD3+/CD8−), T-cytotoxic (CD3+/CD8+), and CD163+ cells was performed on skin biopsies. Results. The results pinpoint targets, such as transforming growth factor β1, as some of the mechanisms underlying disease progression, which may have the potential to improve patient prognostication and the development of precision medicine efforts. Conclusions: We propose that in patients with MF, the evolution of the malignant clone and the associated immune response need to be studied jointly to define relevant strategies for intervention. [ABSTRACT FROM AUTHOR]

Madin–Darby Canine Kidney (MDCK) cells are a key cell line for influenza vaccine production, due to their high viral yield and low mutation resistance. In our laboratory, we established a tertiary cell bank (called M60) using a standard MDCK cell line imported from American Type Culture Collection (ATCC) in the USA. Due to their controversial tumourigenicity, we domesticated non-tumourigenic MDCK cells (named CL23) for influenza vaccine production via monoclonal screening in the early stage of this study, and the screened CL23 cells were characterised based on their low proliferative capacity, which had certain limitations in terms of expanding their production during cell resuscitation. It was thus our objective to enhance the proliferation efficiency of MDCK cells for influenza vaccine production following cell resuscitation, with a view to improving the production of non-tumourigenic MDCK cells for vaccines and enhancing the production of influenza virus lysate vaccines from MDCK cells through genetic intervention. We concentrated on the protein thrombosponin-1 (THBS1), which was markedly differentiated in the proteomics data of the two MDCK cells. By integrating this finding with related studies, we were able to ascertain that THBS1 exerts a significant influence on the level of cell proliferation and apoptosis. Consequently, our objective was to investigate the impact of THBS1 expression on MDCK cell apoptosis by verifying the differences in THBS1 expression between the two MDCK cells and by interfering with THBS1 expression in the MDCK cells. We found that the knockdown of THBS1 significantly increased the proliferation and apoptosis of CL23 cells without causing significant changes in cell migration and invasion, and its overexpression significantly decreased the proliferation of M60 cells and increased cell migration, invasion, and apoptosis. In addition, the TGF-β/Smad pathway target genes transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 2 (Smad2), and mothers against decapentaplegic homolog 3 (Smad3), were significantly down-regulated in CL23 cells after THBS1 knockdown and up-regulated in M60 cells after overexpression, with consistent expression identified at both the mRNA and protein levels. The treatment of cells with TGF-β activators and inhibitors further demonstrated that THBS1 regulated MDCK cell proliferation and apoptosis through the TGF-β/Smad signalling pathway. Finally, we found that THBS1 also regulated H1N1 influenza virus replication. These findings enable a comprehensive understanding of the regulatory mechanisms of THBS1 regarding MDCK cell proliferation and apoptosis functions and the effects of influenza virus replication. [ABSTRACT FROM AUTHOR]

Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations in cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with the ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As a result, pharmacologic inhibition of mIDH has become an attractive therapeutic strategy in CCAs harboring this mutation. One such inhibitor, ivosidenib, has already undergone clinical validation and received FDA approval in this disease, but there is still much work to be done to improve outcomes in mIDH CCA patients. In this publication we will review the pathogenesis and treatment of mIDH CCA with special emphasis on novel agents and combinations currently under investigation. [ABSTRACT FROM AUTHOR]

Background: Social and emotional learning (SEL) is crucial for developing skills such as emotional regulation, cooperation, and goal achievement. Deficits in these skills are linked to later academic and behavioral problems. While SEL interventions have been widely implemented internationally, few have been tested in early childhood settings in Japan, and their effectiveness remains unclear. In 2022, the Fun FRIENDS social and emotional learning program was introduced in class units for 4–5-year-olds attending kindergartens and children's schools in Wakayama Prefecture, Japan. Thus, this study examined the effectiveness of the Fun FRIENDS program in children aged 4–5 years in Japan. Methods: Fun FRIENDS is based on a cognitive-behavioral approach designed to teach participants how to cope with anxiety and stress, and to develop resilience and confidence. The program consists of 10 weekly sessions of approximately 1 h each. The intervention group comprised 115 children from two facilities, while the control group comprised 93 children from three facilities. Intervention effectiveness was evaluated through changes in externalizing (e.g., aggression, oppositional behavior) and internalizing behaviors (e.g., anxiety, depression), measured using the Strengths and Difficulties Questionnaire. Finally, data from 94 participants in the intervention group and 66 participants in the control group were analyzed. Results: In the intervention group, externalizing behaviors showed a significant reduction both before and after the intervention and internalizing behaviors also decreased significantly. Conversely, the control group did not exhibit any significant changes in either externalizing or internalizing behaviors before or after the intervention. The effect size for externalizing behaviors in the target group was 0.744, while the effect size for internalizing behaviors was 0.653. Conclusions: Social and emotional learning programs in classrooms may effectively control problem behaviors in early childhood and prevent school maladjustment. A whole-class approach can reach more children, maximizing the preventive effects. The program can improve academic performance and social adaptation, contributing to the long-term development of psychological health and social skills. Nevertheless, further longitudinal research is required to assess the program's long-term effects. In summary, strengthening the focus on social-emotional learning in early childhood education policy is key to realizing long-term benefits for child development. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a chronic disorder characterized by kidney fibrosis and extracellular matrix accumulation that can lead to end-stage kidney disease. Epithelial-to-mesenchymal transition, inflammatory cytokines, the TGF-β pathway, Wnt/β-catenin signaling, the Notch pathway, and the NF-κB pathway all play crucial roles in the progression of fibrosis. Current medications, such as renin–angiotensin–aldosterone system inhibitors, try to delay disease development but do not stop or reverse fibrosis. This review emphasizes the growing need for tailored antifibrotic medications for CKD treatment. Precision medicine, which combines proteomic, metabolomic, and genetic data, provides a practical way to personalize treatment regimens. Proteomic signatures, such as CKD273, and genetic markers, such as APOL1 and COL4A5, help in patient stratification and focused therapy development. Two recently developed antifibrotic medications, nintedanib and pirfenidone, have been proven to diminish fibrosis in preclinical animals. Additionally, research is being conducted on the efficacy of investigational drugs targeting CTGF and galectin-3 in the treatment of kidney fibrosis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of varying the formulation of a specific peptide hydrogel (PepGel) on the release kinetics of rhBMP-2 in vitro. Three PepGel formulations were assessed: (1) 50% v/v (peptides volume/total volume) PepGel, where synthetic peptides were mixed with crosslinking reagents and rhBMP-2 solution; (2) 67% v/v PepGel; (3) 80% v/v PepGel. Each sample was loaded with 12 µg of rhBMP-2 and incubated in PBS. Released rhBMP-2 was quantified by ELISA at 1 h, 6 h, and 1, 2, 4, 7, 10, 14, and 21 days. To explore how PepGel formulations influence rhBMP-2 release, the gel porosities, swelling ratios, and mechanical properties of the three PepGel formulations were quantitatively analyzed. The results showed that rhBMP-2 encapsulated with 50% v/v PepGel exhibited a sustained release over the 21-day experiment, while the 67% and 80% v/v PepGels demonstrated significantly lower rhBMP-2 release rates compared to the 50% formulation after day 7. Higher histological porosity of PepGel was significantly correlated with increased rhBMP-2 release rates. Conversely, the swelling ratio and elastic modulus of the 50% v/v PepGel were significantly lower than that of the 67% and 80% v/v formulations. In conclusion, this study indicates that varying the formulation of crosslinked PepGel can control rhBMP-2 release rates in vitro by modulating gel porosity, swelling ratio, and mechanical properties. Encapsulation with 50% v/v PepGel offers a sustained rhBMP-2 release pattern in vitro; if replicated in vivo, this could mitigate the adverse effects associated with burst release of rhBMP-2 in clinical applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine multicentric lymphoma is a common neoplasm in dogs, and there is a need to discover diagnostic and prognostic biomarkers to aid veterinarians and pet owners in decision making. Although some protein biomarkers have been identified in the blood of dogs with multicentric lymphoma, there is still a need for new biomarkers are still required to predict the treatment outcome. This study investigated a novel protein biomarker called YKL-40, which is regarded as a prognostic biomarker in human cancers. YKL-40 could be detected in the blood or neoplastic cells. This study assessed the diagnostic and prognostic abilities of blood YKL-40. The findings from thirty dogs with multicentric lymphoma suggest that serum YKL-40 had the disease's severity in canine multicentric lymphoma. However, its ability to predict clinical outcome remains uncertain. Further large-scale studies are required to clarify the role of YKL-40 in canine multicentric lymphoma. YKL-40, a secretory glycoprotein, is known as a prognostic biomarker in human cancers, but its role in canine multicentric lymphoma is not well understood. This study aimed to investigate serum YKL-40 levels in thirty dogs with multicentric lymphoma to determine their prognostic value, association with patient characteristics, and potential to predict chemotherapy response. Serum samples were collected before, during, and after chemotherapy, and YKL-40 level was measured using ELISA. The results showed that the pretreatment serum YKL-40 levels were significantly higher in dogs with multicentric lymphoma (394.0 pg/mL, n = 30) than in healthy controls (218.6 pg/mL, n = 11) (p = 0.012). While a cutoff value of 445.1 pg/mL was observed, further studies are needed to clarify its diagnostic utility. Dogs with clinical stage V had the highest YKL-40 levels (p = 0.027), potentially reflecting disease severity. Furthermore, YKL-40 levels decreased after chemotherapy (p = 0.030). However, YKL-40 levels showed no significant association with progression-free survival (PFS) (HR = 0.93, p = 0.830) or overall survival (OS) (HR = 0.99, p = 0.267). In conclusion, serum YKL-40 levels may potentially detect the disease severity, but its prognostic role remains uncertain. Further studies are required to evaluate serum YKL-40 levels as a potential indicator of treatment response or disease recurrence. [ABSTRACT FROM AUTHOR]