A digital workflow for designing and manufacturing metal frameworks and removable partial dentures: A novel dental technique.

The purpose of this technical report is to demonstrate a fully digital workflow for designing and fabricating metal frameworks and removable partial dentures. After obtaining a digital cast of the dental arch with bilateral distal extension defect, computer-aided design software and 3D printing technology are used for the design and fabrication of the removable partial denture frameworks, denture teeth, and denture bases, instead of the traditional workflow. The assembly of the three components is facilitated through a meticulously structured framework. The technology, which prints metal frameworks, denture bases, and denture teeth through different processes with different materials, achieves full 3D printing technology for making removable partial dentures.

Roles of TRP and PIEZO receptors in autoimmune diseases.

Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.

Microglial ApoD-induced NLRC4 inflammasome activation promotes Alzheimer's disease progression.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease with no effective therapies. It is well known that chronic neuroinflammation plays a critical role in the onset and progression of AD. Well-balanced neuronal-microglial interactions are essential for brain functions. However, determining the role of microglia-the primary immune cells in the brain-in neuroinflammation in AD and the associated molecular basis has been challenging. METHODS: Inflammatory factors in the sera of AD patients were detected and their association with microglia activation was analyzed. The mechanism for microglial inflammation was investigated. IL6 and TNF-α were found to be significantly increased in the AD stage. RESULTS: Our analysis revealed that microglia were extensively activated in AD cerebra, releasing sufficient amounts of cytokines to impair the neural stem cells (NSCs) function. Moreover, the ApoD-induced NLRC4 inflammasome was activated in microglia, which gave rise to the proinflammatory phenotype. Targeting the microglial ApoD promoted NSC self-renewal and inhibited neuron apoptosis. These findings demonstrate the critical role of ApoD in microglial inflammasome activation, and for the first time reveal that microglia-induced inflammation suppresses neuronal proliferation. CONCLUSION: Our studies establish the cellular basis for microglia activation in AD progression and shed light on cellular interactions important for AD treatment.

Case report and literature review: plexiform schwannoma in the penile and inguinal region in a child.

Penile schwannoma is an uncommonly seen peripheral nerve tumor, of which penile plexiform schwannomas (PS) is extremely rare that has only been reported in several adults. We present a case of penile PS with a similar lesion in inguinal region in a 9-year-old child, which appeared as painless masses and rapidly growing within one year. Penile ultrasonography suggested well-defined lesions with limited vascularity. Both masses presented with low-to-intermediated signal intensity and no definite enhancement in computed tomography. The lesions were completely resected with minimal intraoperative bleeding, and a diagnose of benign PS was confirmed based on H&E staining and positive S-100 expression in immunohistochemistry. There was no evidence of tumor recurrence or metastasis after 6 months of follow-up. Only 6 cases of penile schwannoma in children were recorded, of which 5 were malignant, and none was PS. The malignancy rate of penile schwannoma in children may be overestimated due to delayed diagnose of benign ones. A rapidly growing penile mass with a suspected metastatic lesion in inguinal region could be easily misdiagnosed as malignant. This case report and literature review is expected to assist clinicians in getting a comprehensive understanding of children penile schwannomas and choosing the best management strategy when faced with this rare condition.

Combining magnetic resonance fingerprinting with voxel-based morphometric analysis to reduce false positives for focal cortical dysplasia detection.

OBJECTIVE: We aim to improve focal cortical dysplasia (FCD) detection by combining high-resolution, three-dimensional (3D) magnetic resonance fingerprinting (MRF) with voxel-based morphometric magnetic resonance imaging (MRI) analysis. METHODS: We included 37 patients with pharmacoresistant focal epilepsy and FCD (10 IIa, 15 IIb, 10 mild Malformation of Cortical Development [mMCD], and 2 mMCD with oligodendroglial hyperplasia and epilepsy [MOGHE]). Fifty-nine healthy controls (HCs) were also included. 3D lesion labels were manually created. Whole-brain MRF scans were obtained with 1 mm3 isotropic resolution, from which quantitative T1 and T2 maps were reconstructed. Voxel-based MRI postprocessing, implemented with the morphometric analysis program (MAP18), was performed for FCD detection using clinical T1w images, outputting clusters with voxel-wise lesion probabilities. Average MRF T1 and T2 were calculated in each cluster from MAP18 output for gray matter (GM) and white matter (WM) separately. Normalized MRF T1 and T2 were calculated by z-scores using HCs. Clusters that overlapped with the lesion labels were considered true positives (TPs); clusters with no overlap were considered false positives (FPs). Two-sample t-tests were performed to compare MRF measures between TP/FP clusters. A neural network model was trained using MRF values and cluster volume to distinguish TP/FP clusters. Ten-fold cross-validation was used to evaluate model performance at the cluster level. Leave-one-patient-out cross-validation was used to evaluate performance at the patient level. RESULTS: MRF metrics were significantly higher in TP than FP clusters, including GM T1, normalized WM T1, and normalized WM T2. The neural network model with normalized MRF measures and cluster volume as input achieved mean area under the curve (AUC) of .83, sensitivity of 82.1%, and specificity of 71.7%. This model showed superior performance over direct thresholding of MAP18 FCD probability map at both the cluster and patient levels, eliminating ≥75% FP clusters in 30% of patients and ≥50% of FP clusters in 91% of patients. SIGNIFICANCE: This pilot study suggests the efficacy of MRF for reducing FPs in FCD detection, due to its quantitative values reflecting in vivo pathological changes. © 2024 International League Against Epilepsy.

Combined Use of Endoscopic Techniques and Virtual Surgical Planning for Intraoral Approach for Hemi-mandibular Resection and Reconstruction.

Background: The study aimed to describe our experience in using endoscopic procedures to aid hemi-mandibular reconstruction with bone flaps through transoral approach. Methods: Five patients with huge benign mandibular tumors underwent transoral mandibulectomy and hemi-mandibular reconstruction, using endoscopy. Facial symmetry, occlusion, bone healing, and mandibular similarity were all evaluated postoperatively. The paired-samples t test was used to compare quantitative data, and a P value less than 0.05 was considered a significant difference. Results: All five patients who received transoral mandibular surgery recovered in terms of TMJ functionality, facial symmetry, and aesthetic results. Endoscopy monitored and ensured that bone flaps were correctly connected and fixed. The accuracy of endoscopy-guided mandibular reconstruction was confirmed by quantitative examination for four cases, which revealed no statistically significant variations between postoperative CT analysis and preoperative virtual surgical planning data. Conclusions: Endoscopy-assisted virtual surgery may resolve concerns with transoral hemi-mandibular reconstruction and broaden indications for mini-invasive mandibular reconstruction. However, only patients with benign mandibular tumors were included in our study, so surgeons should be very cautious if applying this technique to malignant lesions or bony tumors invading soft tissues.

Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. METHODS: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. RESULTS: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. CONCLUSIONS: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.

Coordinate-based data analysis of the accuracy of five intraoral scanners for scanning completely dentate and partially edentulous mandibular arches.

STATEMENT OF PROBLEM: Current methods for assessing the accuracy of intraoral scanners (IOSs) that reduce errors and provide comprehensive data compared with previous methods are lacking. PURPOSE: The purpose of this in vitro study was to present a coordinate-based data analysis method to compare the accuracy of 5 IOSs for scanning completely dentate and partially edentulous casts. MATERIAL AND METHODS: Reference scans of 2 complete arch casts (completely and partially dentate) were digitized using a high-precision laboratory scanner (Ceramill Map 600). Each cast was scanned 10 times each using 5 IOSs (3Shape TRIOS 3, Planmeca Emerald, iTero Element 5D, Medit i500, and Shining Aoralscan 3). The dataset of all 10 test groups was analyzed by using a reverse engineering software program (Geomagic Wrap). Each test cast was aligned with the reference cast by 3-dimensional (3D) superimposition to determine the translation and rotation along the x-, y-, and z-axes. The dataset was analyzed using the Kruskal-Wallis and post hoc Bonferroni tests (α=.05). RESULTS: Significant differences were observed in all parameters among all scanners when scanning the same cast (P<.05). Significant differences were observed in at least 1 parameter for all scanners, except Element 5D after scanning different casts using the same scanner. Deviations in the test data generally relocated toward the mesial, buccal, and apical sides, and the casts were almost always rotated clockwise around the y-axis and counterclockwise around the z-axis. For the completely dentate cast, among all IOSs, Element 5D demonstrated the highest accuracy in most of the measured parameters, specifically in the y-axis translation (0.06[0.07] mm), z-axis translation (0.08[0.05] mm), and y-axis rotation (0.21[0.16] degree) (P<.05). For the partially edentulous cast, Element 5D displayed higher accuracy in most of the measured parameters, including the x-axis translation (0.11[0.14] mm) and z-axis rotation (0.12[0.18] degree) (P<.05). Emerald also displayed higher accuracy in most of the measured parameters, including the y-axis translation (0.05[0.08] mm) and y-axis rotation (0.14[0.12] degree) (P<.05). Element 5D exhibited no difference in the scanning accuracy between the 2 types of casts (P>.05). CONCLUSIONS: Element 5D offered a high level of accuracy and was an appropriate scanner for both situations. The method presented in this study provides a good assessment of accuracy deviations in complete arch scans using 3D coordinate-based data analysis.

The quest for nanoparticle-powered vaccines in cancer immunotherapy.

Despite recent advancements in cancer treatment, this disease still poses a serious threat to public health. Vaccines play an important role in preventing illness by preparing the body's adaptive and innate immune responses to combat diseases. As our understanding of malignancies and their connection to the immune system improves, there has been a growing interest in priming the immune system to fight malignancies more effectively and comprehensively. One promising approach involves utilizing nanoparticle systems for antigen delivery, which has been shown to potentiate immune responses as vaccines and/or adjuvants. In this review, we comprehensively summarized the immunological mechanisms of cancer vaccines while focusing specifically on the recent applications of various types of nanoparticles in the field of cancer immunotherapy. By exploring these recent breakthroughs, we hope to identify significant challenges and obstacles in making nanoparticle-based vaccines and adjuvants feasible for clinical application. This review serves to assess recent breakthroughs in nanoparticle-based cancer vaccinations and shed light on their prospects and potential barriers. By doing so, we aim to inspire future immunotherapies for cancer that harness the potential of nanotechnology to deliver more effective and targeted treatments.

Quantifying 3D MR fingerprinting (3D-MRF) reproducibility across subjects, sessions, and scanners automatically using MNI atlases.

PURPOSE: Quantitative MRI techniques such as MR fingerprinting (MRF) promise more objective and comparable measurements of tissue properties at the point-of-care than weighted imaging. However, few direct cross-modal comparisons of MRF's repeatability and reproducibility versus weighted acquisitions have been performed. This work proposes a novel fully automated pipeline for quantitatively comparing cross-modal imaging performance in vivo via atlas-based sampling. METHODS: We acquire whole-brain 3D-MRF, turbo spin echo, and MPRAGE sequences three times each on two scanners across 10 subjects, for a total of 60 multimodal datasets. The proposed automated registration and analysis pipeline uses linear and nonlinear registration to align all qualitative and quantitative DICOM stacks to Montreal Neurological Institute (MNI) 152 space, then samples each dataset's native space through transformation inversion to compare performance within atlas regions across subjects, scanners, and repetitions. RESULTS: Voxel values within MRF-derived maps were found to be more repeatable (σT1 = 1.90, σT2 = 3.20) across sessions than vendor-reconstructed MPRAGE (σT1w = 6.04) or turbo spin echo (σT2w = 5.66) images. Additionally, MRF was found to be more reproducible across scanners (σT1 = 2.21, σT2 = 3.89) than either qualitative modality (σT1w = 7.84, σT2w = 7.76). Notably, differences between repeatability and reproducibility of in vivo MRF were insignificant, unlike the weighted images. CONCLUSION: MRF data from many sessions and scanners can potentially be treated as a single dataset for harmonized analysis or longitudinal comparisons without the additional regularization steps needed for qualitative modalities.

3D-printed bioink loading with stem cells and cellular vesicles for periodontitis-derived bone defect repair.

The suitable microenvironment of bone regeneration is critically important for periodontitis-derived bone defect repair. Three major challenges in achieving a robust osteogenic reaction are the exist of oral inflammation, pathogenic bacteria invasion and unaffluent seed cells. Herein, a customizable and multifunctional 3D-printing module was designed with glycidyl methacrylate (GMA) modified epsilon-poly-L-lysine (EPLGMA) loading periodontal ligament stem cells (PDLSCs) and myeloid-derived suppressive cells membrane vesicles (MDSCs-MV) bioink (EPLGMA/PDLSCs/MDSCs-MVs, abbreviated as EPM) for periodontitis-derived bone defect repair. The EPM showed excellent mechanical properties and physicochemical characteristics, providing a suitable microenvironment for bone regeneration.In vitro, EPMs presented effectively kill the periodontopathic bacteria depend on the natural antibacterial properties of the EPL. Meanwhile, MDSCs-MV was confirmed to inhibit T cells through CD73/CD39/adenosine signal pathway, exerting an anti-inflammatory role. Additionally, seed cells of PDLSCs provide an adequate supply for osteoblasts. Moreover, MDSCs-MV could significantly enhance the mineralizing capacity of PDLSCs-derived osteoblast. In the periodontal bone defect rat model, the results of micro-CT and histological staining demonstrated that the EPM scaffold similarly had an excellent anti-inflammatory and bone regeneration efficacyin vivo. This biomimetic and multifunctional 3D-printing bioink opens new avenues for periodontitis-derived bone defect repair and future clinical application.

Automated Prediction of Infant Cognitive Development Risk by Video: A Pilot Study.

OBJECTIVE: Cognition is an essential human function, and its development in infancy is crucial. Traditionally, pediatricians used clinical observation or medical imaging to assess infants' current cognitive development (CD) status. The object of pediatricians' greater concern is however their future outcomes, because high-risk infants can be identified early in life for intervention. However, this opportunity has not yet been realized. Fortunately, some recent studies have shown that the general movement (GM) performance of infants around 3-4 months after birth might reflect their future CD status, which gives us an opportunity to achieve this goal by cameras and artificial intelligence. METHODS: First, infants' GM videos were recorded by cameras, from which a series of features reflecting their bilateral movement symmetry (BMS) were extracted. Then, after at least eight months of natural growth, the infants' CD status was evaluated by the Bayley Infant Development Scale, and they were divided into high-risk and low-risk groups. Finally, the BMS features extracted from the early recorded GM videos were fed into the classifiers, using late infant CD risk assessment as the prediction target. RESULTS: The area under the curve, recall and precision values reached 0.830, 0.832, and 0.823 for two-group classification, respectively. CONCLUSION: This pilot study demonstrates that it is possible to automatically predict the CD of infants around the age of one year based on their GMs recorded early in life. SIGNIFICANCE: This study not only helps clinicians better understand infant CD mechanisms, but also provides an economical, portable and non-invasive way to screen infants at high-risk early to facilitate their recovery.

An Evidence Map of Clinical Practice Guideline Recommendations and Quality on Venous Leg Ulcer.

Significance: Venous leg ulcers (VLUs) are the most common venous disease, mainly presenting as open skin lesions on the legs or feet and are an important concern in clinical care settings. Recent Advances: Comprehensive tactics were employed to search electronic databases PubMed, Embase, guideline databases, and society websites were searched for Clinical Practice Guidelines (CPGs) on VLU care. The basic information, recommendations for the VLUs, methodological quality, and reporting quality of VLU's CPGs were extracted and captured in Excel. The quality of each CPG was independently assessed by four researchers using AGREE II instrument and the RIGHT checklist. Critical Issues: This study included 19 CPGs with a combined 23 recommendations. The assessment of VLUs was summarized based on the recommendations of VLUs in 11 major items; six on VLU's diagnosis and six on therapeutic strategies of VLUs. The identified CPGs were of mixed quality, and the highest score based on the scope and purpose was 82.85 ± 11.66, whereas the lowest mean score based on the editorial independence by AGREE II was 59.93 ± 21.50. Regarding the RIGHT checklist, field one (basic information) had the highest reporting rate (84.33%), whereas field five (review and quality assurance) had the lowest quality of CPGs (41.11%). Future Directions: This evidence map provided new perspectives in the presentation of evidence. In addition, the evidence map collected and evaluated the characteristics of published CPGs. Thus, the evidence map enhances our knowledge and promotes the development of trustworthy CPGs for VLUs.

Small peptide signaling via OsCIF1/2 mediates Casparian strip formation at the root endodermal and nonendodermal cell layers in rice.

The Casparian strip (CS) is a ring-like lignin structure deposited between endodermal cells that forms an apoplastic barrier to control the selective uptake of nutrients in vascular plants. However, the molecular mechanism of CS formation in rice (Oryza sativa), which possesses one CS each in the endodermis and exodermis, is relatively unknown. Here, we functionally characterized CS INTEGRITY FACTOR1 (OsCIF1a, OsCIF1b), OsCIF2, and SCHENGEN3 (OsSGN3a, OsSGN3b) in rice. OsCIF1s and OsCIF2 were mainly expressed in the stele, while OsSGN3s localized around the CS at the endodermis. Knockout of all three OsCIFs or both OsSGN3s resulted in a discontinuous CS and a dramatic reduction in compensatory (less localized) lignification and suberization at the endodermis. By contrast, ectopic overexpression of OsCIF1 or OsCIF2 induced CS formation as well as overlignification and oversuberization at single or double cortical cell layers adjacent to the endodermis. Ectopic co-overexpression of OsCIF1 and SHORTROOT1 (OsSHR1) induced the formation of more CS-like structures at multiple cortical cell layers. Transcriptome analysis identified 112 downstream genes modulated by the OsCIF1/2-OsSGN3 signaling pathway, which is involved in CS formation and activation of the compensatory machinery in native endodermis and nonnative endodermis-like cell layers. Our results provide important insights into the molecular mechanism of CIF-mediated CS formation at the root endodermal and nonendodermal cell layers.

Bone marrow adipocyte: Origin, biology and relationship with hematological malignancy.

Bone marrow adipose tissue (BMAT) has been histologically recognized for decades. In this study, we performed a bibliometric analysis to quantitatively analyze the clusters of keywords of BMAT and hematopoiesis to better understand BMAT and hematopoiesis. Starting with conclusive keywords, our results demonstrated that BMAds is distinct from extramedullary adipose tissues and maintains a routine but dynamic accumulation throughout an individual's life. Various pathophysiological factors take part in dysregulation of the adipose-osteogenic balance throughout life. Bone marrow adipocytes (BMAds) are also contradictorily involved in normal hematopoiesis, and positively participate in the occurrence and progression of hematologic malignancies, exerting a chemoprotective role in tumor treatment. Mechanically, metabolic reprogramming and abnormal secretory profile of BMAds and tumor cells play a critical role in the chemotherapy resistance. Overall, we hope that this work will provide new ideas for relevant future research on BMAds.

Self-calibrated subspace reconstruction for multidimensional MR fingerprinting for simultaneous relaxation and diffusion quantification.

PURPOSE: To propose a new reconstruction method for multidimensional MR fingerprinting (mdMRF) to address shading artifacts caused by physiological motion-induced measurement errors without navigating or gating. METHODS: The proposed method comprises two procedures: self-calibration and subspace reconstruction. The first procedure (self-calibration) applies temporally local matrix completion to reconstruct low-resolution images from a subset of under-sampled data extracted from the k-space center. The second procedure (subspace reconstruction) utilizes temporally global subspace reconstruction with pre-estimated temporal subspace from low-resolution images to reconstruct aliasing-free, high-resolution, and time-resolved images. After reconstruction, a customized outlier detection algorithm was employed to automatically detect and remove images corrupted by measurement errors. Feasibility, robustness, and scan efficiency were evaluated through in vivo human brain imaging experiments. RESULTS: The proposed method successfully reconstructed aliasing-free, high-resolution, and time-resolved images, where the measurement errors were accurately represented. The corrupted images were automatically and robustly detected and removed. Artifact-free T1, T2, and ADC maps were generated simultaneously. The proposed reconstruction method demonstrated robustness across different scanners, parameter settings, and subjects. A high scan efficiency of less than 20 s per slice has been achieved. CONCLUSION: The proposed reconstruction method can effectively alleviate shading artifacts caused by physiological motion-induced measurement errors. It enables simultaneous and artifact-free quantification of T1, T2, and ADC using mdMRF scans without prospective gating, with robustness and high scan efficiency.

Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma.

Peroxisome proliferator-activated receptor gamma (PPARG), a key transcription factor involved in lipid metabolism and glucose homeostasis, has been implicated in various types of cancer. However, its precise role in cancer remains unclear. In this study, we conducted a comprehensive pan-cancer analysis of PPARG expression using various types of cancer obtained from public databases. We observed significant heterogeneity in PPARG expression across different types of cancer. The association between PPARG expression and patient prognosis was investigated using Cox proportional hazards regression models and survival analysis. Clinical features and protein expression levels in the cohort showed that PPARG expression was strongly associated, suggesting its potential as a therapeutic target. We also evaluated the prognostic potential of PPARG by analyzing immune infiltration and genomic stability. We experimentally validated the potential of PPARG as a therapeutic target by analyzing drug sensitivity profiles, molecular docking simulations, and in vitro cell proliferation assays associated with PPARG expression. We identified common expression patterns of PPARG with other genes involved in key carcinogenic pathways. This provides deeper insights into the molecular mechanisms underlying its carcinogenic role. Additionally, functional enrichment analysis revealed significant enrichment of genes related to drug metabolism, cell proliferation, and immune response pathways associated with PPARG. Our findings highlight the importance of PPARG in the broader biology of cancer and suggest its potential as a diagnostic and therapeutic target for specific types of cancer. The results of our study provide strong support for the potential role of PPARG as a promising prognostic biomarker and immunotherapeutic target across various types of cancer.