Susceptibility of Mangifera indica (Sapindales: Anacardiaceae) cultivars to fruit flies (Diptera: Tephritidae) in 2 agroecological zones of Cameroon.

The Sudano-Sahelian and the high Guinea savannahs agroecological zones of Cameroon are suitable for the full development of tree crops, including mango. Unfortunately, fresh fruits exported to local and international markets are frequently rejected due to the presence of fruit fly larvae (Diptera: Tephritidae), resulting in drastic income losses and overuse of chemical control products. To promote sustainable management strategies, a 2-yr study (2020-2021) was conducted in 4 and 3 mixed orchards, respectively. Attacked mangoes showing signs of fruit fly damage were collected and taken to the laboratory to rear and identify fruit flies. Repeated grafting and agroclimatic differences were responsible for dissimilarities between the 2 zones, with 18 and 16 cultivars, respectively. From 2,857 attacked mangoes, 26,707 fruit flies belonging to 4 species were identified: Bactrocera dorsalis, Ceratitis cosyra, Ceratitis fasciventris, and Ceratitis anonae. Climate change was the factor determining the distribution of the 2 most important mango fruit flies: B. dorsalis was a wetland species (dominance/occurrence > 70%), while C. cosyra was a dry-land species (dominance/occurrence > 75%). Both species were responsible for high levels of infestations. Bactrocera dorsalis preferred 3 mango cultivars, namely Palmer and Smith in Zone 1, and Ifack 1 in Zone 2 (infestation > 20 individuals/100 g of mango). The host-plant spectrum of C. cosyra was modified by alternative host plants. Both C. fasciventris and C. anonae were rare. Findings from this study could guide researchers in the development of monitoring tools for fruit fly populations and, subsequently, in reducing the damage they cause to mangoes.

NGFR regulates stromal cell activation in germinal centers.

Nerve growth factor receptor (NGFR) is expressed by follicular dendritic cells (FDCs). However, the role of NGFR in the humoral response is not well defined. Here, we study the effect of Ngfr loss on lymph node organization and function, demonstrating that Ngfr depletion leads to spontaneous germinal center (GC) formation and an expansion of the GC B cell compartment. In accordance with this effect, stromal cells are altered in Ngfr-/- mice with a higher frequency of FDCs, characterized by CD21/35, MAdCAM-1, and VCAM-1 overexpression. GCs are located ectopically in Ngfr-/- mice, with lost polarization together with impaired high-affinity antibody production and an increase in circulating autoantibodies. We observe higher levels of autoantibodies in Bcl2 Tg/Ngfr-/- mice, concomitant with a higher incidence of autoimmunity and lower overall survival. Our work shows that NGFR is involved in maintaining GC structure and function, participating in GC activation, antibody production, and immune tolerance.

Autonomous System for Tumor Resection (ASTR) - Dual-Arm Robotic Midline Partial Glossectomy.

Head and neck cancers are the seventh most common cancers worldwide, with squamous cell carcinoma being the most prevalent histologic subtype. Surgical resection is a primary treatment modality for many patients with head and neck squamous cell carcinoma, and accurately identifying tumor boundaries and ensuring sufficient resection margins are critical for optimizing oncologic outcomes. This study presents an innovative autonomous system for tumor resection (ASTR) and conducts a feasibility study by performing supervised autonomous midline partial glossectomy for pseudotumor with millimeter accuracy. The proposed ASTR system consists of a dual-camera vision system, an electrosurgical instrument, a newly developed vacuum grasping instrument, two 6-DOF manipulators, and a novel autonomous control system. The letter introduces an ontology-based research framework for creating and implementing a complex autonomous surgical workflow, using the glossectomy as a case study. Porcine tongue tissues are used in this study, and marked using color inks and near-infrared fluorescent (NIRF) markers to indicate the pseudotumor. ASTR actively monitors the NIRF markers and gathers spatial and color data from the samples, enabling planning and execution of robot trajectories in accordance with the proposed glossectomy workflow. The system successfully performs six consecutive supervised autonomous pseudotumor resections on porcine specimens. The average surface and depth resection errors measure 0.73±0.60 mm and 1.89±0.54 mm, respectively, with no positive tumor margins detected in any of the six resections. The resection accuracy is demonstrated to be on par with manual pseudotumor glossectomy performed by an experienced otolaryngologist.

Reconstruction of dental roots for implant planning purposes: a retrospective computational and radiographic assessment of single-implant cases.

PURPOSE: The aim of the study was to assess the deviation between clinical implant axes (CIA) determined by a surgeon during preoperative planning and reconstructed tooth axes (RTA) of missing teeth which were automatically computed by a previously introduced anatomical SSM. METHODS: For this purpose all available planning datasets of single-implant cases of our clinic, which were planned with coDiagnostix Version 9.9 between 2018 and 2021, were collected for retrospective investigation. Informed consent was obtained. First, the intraoral scans of implant patients were annotated and subsequently analyzed using the SSM. The RTA, computed by the SSM, was then projected into the preoperative planning dataset. The amount and direction of spatial deviation between RTA and CIA were then measured. RESULTS: Thirty-five patients were implemented. The mean distance between the occlusal entry point of anterior and posterior implants and the RTA was 0.99 mm ± 0.78 mm and 1.19 mm ± 0.55, respectively. The mean angular deviation between the CIA of anterior and posterior implants and the RTA was 12.4° ± 3.85° and 5.27° ± 2.97° respectively. The deviations in anterior implant cases were systematic and could be corrected by computing a modified RTA (mRTA) with decreased deviations (0.99 mm ± 0.84 and 4.62° ± 1.95°). The safety distances of implants set along the (m)RTA to neighboring teeth were maintained in 30 of 35 cases. CONCLUSION: The RTA estimated by the SSM revealed to be a viable implant axis for most of the posterior implant cases. As there are natural differences between the anatomical tooth axis and a desirable implant axis, modifications were necessary to correct the deviations which occurred in anterior implant cases. However, the presented approach is not applicable for clinical use and always requires manual optimization by the planning surgeon.

X-Linked Hypophosphatemia: Does Targeted Therapy Modify Dental Impairment?

X-linked hypophosphatemia is a rare, hereditary disorder that significant influences teeth and alveolar bone. The first clinical sign leading to the diagnosis of X-linked hypophosphatemia is often dental impairment with dental abscesses and dentin mineralization defects. Genetic analysis helped find the responsible gene and therefore opened up new ways of therapeutically managing X-linked hypophosphatemia. The human monoclonal antibody Burosumab represents a milestone in the targeted therapy of this hereditary disease by directly addressing its pathophysiology. Targeted therapy has been shown to improve skeletal impairment, pain, and phosphate metabolism. However, the influence of this new therapy on dental impairment has only been addressed in a few recent studies with varying results. Therefore, in this review, we aim to summarize the dental phenotype and analyze the different treatment modalities with a focus on dental impairment.

KDM6B drives epigenetic reprogramming associated with lymphoid stromal cell early commitment and immune properties.

Mature lymphoid stromal cells (LSCs) are key organizers of immune responses within secondary lymphoid organs. Similarly, inflammation-driven tertiary lymphoid structures depend on immunofibroblasts producing lymphoid cytokines and chemokines. Recent studies have explored the origin and heterogeneity of LSC/immunofibroblasts, yet the molecular and epigenetic mechanisms involved in their commitment are still unknown. This study explored the transcriptomic and epigenetic reprogramming underlying LSC/immunofibroblast commitment. We identified the induction of lysine demethylase 6B (KDM6B) as the primary epigenetic driver of early immunofibroblast differentiation. In addition, we observed an enrichment for KDM6B gene signature in murine inflammatory fibroblasts and pathogenic stroma of patients with autoimmune diseases. Last, KDM6B was required for the acquisition of LSC/immunofibroblast functional properties, including the up-regulation of CCL2 and the resulting recruitment of monocytes. Overall, our results reveal epigenetic mechanisms that participate in the early commitment and immune properties of immunofibroblasts and support the use of epigenetic modifiers as fibroblast-targeting strategies in chronic inflammation.

Automated detection of cephalometric landmarks using deep neural patchworks.

OBJECTIVES: This study evaluated the accuracy of deep neural patchworks (DNPs), a deep learning-based segmentation framework, for automated identification of 60 cephalometric landmarks (bone-, soft tissue- and tooth-landmarks) on CT scans. The aim was to determine whether DNP could be used for routine three-dimensional cephalometric analysis in diagnostics and treatment planning in orthognathic surgery and orthodontics. METHODS: Full skull CT scans of 30 adult patients (18 female, 12 male, mean age 35.6 years) were randomly divided into a training and test data set (each n = 15). Clinician A annotated 60 landmarks in all 30 CT scans. Clinician B annotated 60 landmarks in the test data set only. The DNP was trained using spherical segmentations of the adjacent tissue for each landmark. Automated landmark predictions in the separate test data set were created by calculating the center of mass of the predictions. The accuracy of the method was evaluated by comparing these annotations to the manual annotations. RESULTS: The DNP was successfully trained to identify all 60 landmarks. The mean error of our method was 1.94 mm (SD 1.45 mm) compared to a mean error of 1.32 mm (SD 1.08 mm) for manual annotations. The minimum error was found for landmarks ANS 1.11 mm, SN 1.2 mm, and CP_R 1.25 mm. CONCLUSION: The DNP-algorithm was able to accurately identify cephalometric landmarks with mean errors <2 mm. This method could improve the workflow of cephalometric analysis in orthodontics and orthognathic surgery. Low training requirements while still accomplishing high precision make this method particularly promising for clinical use.

Learning analytics for lifelong career development: a framework to support sustainable formative assessment and self-reflection in programs developing career self-efficacy.

Among myriad complex challenges facing educational institutions in this era of a rapidly evolving job marketplace is the development of career self-efficacy among students. Self-efficacy has traditionally been understood to be developed through the direct experience of competence, the vicarious experience of competence, social persuasion, and physiological cues. These four factors, and particularly the first two, are difficult to build into education and training programs in a context where changing skills make the specific meaning of graduate competence largely unknown and, notwithstanding the other contributions in this collection, largely unknowable. In response, in this paper we argue for a working metacognitive model of career self-efficacy that will prepare students with the skills needed to evaluate their skills, attitudes and values and then adapt and develop them as their career context evolves around them. The model we will present is one of evolving complex sub-systems within an emergent milieu. In identifying various contributing factors, the model provides specific cognitive and affective constructs as important targets for actionable learning analytics for career development.

Single-cell Deconvolution of a Specific Malignant Cell Population as a Poor Prognostic Biomarker in Low-risk Clear Cell Renal Cell Carcinoma Patients.

BACKGROUND: Intratumor heterogeneity (ITH) is a key feature in clear cell renal cell carcinomas (ccRCCs) that impacts outcomes such as aggressiveness, response to treatments, or recurrence. In particular, it may explain tumor relapse after surgery in clinically low-risk patients who did not benefit from adjuvant therapy. Recently, single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to unravel expression ITH (eITH) and might enable better assessment of clinical outcomes in ccRCC. OBJECTIVE: To explore eITH in ccRCC with a focus on malignant cells (MCs) and assess its relevance to improve prognosis for low-risk patients. DESIGN, SETTING, AND PARTICIPANTS: We performed scRNA-seq on tumor samples from five untreated ccRCC patients ranging from pT1a to pT3b. Data were complemented with a published dataset composed of pairs of matched normal and ccRCC samples. INTERVENTION: Radical or partial nephrectomy on untreated ccRCC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Viability and cell type proportions were determined by flow cytometry. Following scRNA-seq, a functional analysis was performed and tumor progression trajectories were inferred. A deconvolution approach was applied on an external cohort, and Kaplan-Meier survival curves were estimated with respect to the prevalence of malignant clusters. RESULTS AND LIMITATIONS: We analyzed 54 812 cells and identified 35 cell subpopulations. The eITH analysis revealed that each tumor contained various degrees of clonal diversity. The transcriptomic signatures of MCs in one particularly heterogeneous sample were used to design a deconvolution-based strategy that allowed the risk stratification of 310 low-risk ccRCC patients. CONCLUSIONS: We described eITH in ccRCCs, and used this information to establish significant cell population-based prognostic signatures and better discriminate ccRCC patients. This approach has the potential to improve the stratification of clinically low-risk patients and their therapeutic management. PATIENT SUMMARY: We sequenced the RNA content of individual cell subpopulations composed of clear cell renal cell carcinomas and identified specific malignant cells the genetic information of which can be used to predict tumor progression.

Donor site morbidity after computer assisted surgical reconstruction of the mandible using deep circumflex iliac artery grafts: a cross sectional study.

BACKGROUND: Computer Assisted Design and Computer Assisted Manufacturing (CAD/CAM) have revolutionized oncologic surgery of the head and neck. A multitude of benefits of this technique has been described, but there are only few reports of donor site comorbidity following CAD/CAM surgery. METHODS: This study investigated comorbidity of the hip following deep circumflex iliac artery (DCIA) graft raising using CAD/CAM techniques. A cross-sectional examination was performed to determine range of motion, muscle strength and nerve disturbances. Furthermore, correlations between graft volume and skin incision length with postoperative donor site morbidity were assessed using Spearman's rank correlation, linear regression and analysis of variance (ANOVA). RESULTS: Fifteen patients with a mean graft volume of 21.2 ± 5.7 cm3 and a mean incision length of 228.0 ± 30.0 mm were included. Patients reported of noticeable physical limitations in daily life activities (12.3 ± 11.9 weeks) and athletic activities (38.4 ± 40.0 weeks in mean) following surgery. Graft volume significantly correlated with the duration of the use of walking aids (R = 0.57; p = 0.033) and impairment in daily life activities (R = 0.65; p = 0.012). The length of the scar of the donor-site showed a statistically significant association with postoperative iliohypogastric nerve deficits (F = 4.4, p = 0.037). Patients with anaesthaesia of a peripheral cutaneous nerve had a larger mean scar length (280 ± 30.0 mm) than subjects with hypaesthesia (245 ± 10.1 mm) or no complaints (216 ± 27.7 mm). CONCLUSIONS: Despite sophisticated planning options in modern CAD/CAM surgery, comorbidity of the donor site following  iliac graft harvesting is still a problem. This study is the first to investigate comorbidity after DCIA graft raising in a patient group treated exclusively with CAD/CAM techniques. The results indicate that a minimal invasive approach in terms of small graft volumes and small skin incisions could help to reduce postoperative symptomatology. Trial registration Retrospectively registered at the German Clinical Trials Register (DRKS-ID: DRKS00029066); registration date: 23/05/2022.

Designing Maker initiatives for educational inclusion.

The "Maker" movement is a cultural as well as educational phenomenon that has the potential to offer significant opportunities to students in conditions of social, economic and cultural disadvantage. The research reported in this paper, however, suggests that the simple provision of "Maker Spaces" for such activity is simplistic and not sufficient to realise this potential. The research involved a mixed methods study of a cohort of year 7 students (n = 26) in an Australian school located in a socio-economically disadvantaged outer-metropolitan region. The cohort undertook a range of Maker activities at a new "creativity centre" built at the school. Results indicate that the activities had positive impact on student attitudes towards science, technology, engineering and mathematics (STEM) overall, but that the impact was highly specific across attitudinal constructs. A strong ranging effect was also evident, suggesting that the impact of the experience was highly dependent on students' initial attitudes. Reflecting on these results, the paper also offers a reference framework that may help keep equity in mind when designing different kinds of Maker experience.

Distinct B-Cell Specific Transcriptional Contexts of the BCL2 Oncogene Impact Pre-Malignant Development in Mouse Models.

Upregulated expression of the anti-apoptotic BCL2 oncogene is a common feature of various types of B-cell malignancies, from lymphoma to leukemia or myeloma. It is currently unclear how the various patterns of deregulation observed in pathology eventually impact the phenotype of malignant B cells and their microenvironment. Follicular lymphoma (FL) is the most common non-Hodgkin lymphoma arising from malignant germinal center (GC) B-cells, and its major hallmark is the t(14:18) translocation occurring in B cell progenitors and placing the BCL2 gene under the control of the immunoglobulin heavy chain locus regulatory region (IgH 3'RR), thus exposing it to constitutive expression and hypermutation. Translocation of BCL2 onto Ig light chain genes, BCL2 gene amplification, and other mechanisms yielding BCL2 over-expression are, in contrast, rare in FL and rather promote other types of B-cell lymphoma, leukemia, or multiple myeloma. In order to assess the impact of distinct BCL2 deregulation patterns on B-cell fate, two mouse models were designed that associated BCL2 and its full P1-P2 promoter region to either the IgH 3'RR, within a "3'RR-BCL2" transgene mimicking the situation seen in FL, or an Ig light chain locus context, through knock-in insertion at the Igκ locus ("Igκ-BCL2" model). While linkage to the IgH 3' RR mostly yielded expression in GC B-cells, the Igκ-driven up-regulation culminated in plasmablasts and plasma cells, boosting the plasma cell in-flow and the accumulation of long-lived plasma cells. These data demonstrate that the timing and level of BCL2 deregulation are crucial for the behavior of B cells inside GC, an observation that could strongly impact the lymphomagenesis process triggered by secondary genetic hits.

Feasibility of Implant Strain Measurement for Assessing Mandible Bone Regeneration.

Nonunion is one of the most dreaded complications after operative treatment of mandible fractures or after mandible reconstruction using vascularized and non-vascularized bone grafts. Often diagnosis is made at advanced stage of disease when pain or complications occur. Devices that monitor fracture healing and bone regeneration continuously are therefore urgently needed in the craniomaxillofacial area. One promising approach is the strain measurement of plates. An advanced prototype of an implantable strain measurement device was tested after fixation to a locking mandible reconstruction plate in multiple compression experiments to investigate the potential functionality of strain measurement in the mandibular region. Compression experiments show that strain measurement devices work well under experimental conditions in the mandibular angle and detect plate deformation in a reliable way. For monitoring in the mandibular body, the device used in its current configuration was not suitable. Implant strain measurement of reconstruction plates is a promising methodical approach for permanent monitoring of bone regeneration and fracture healing in the mandible. The method helps to avoid or detect complications at an early point in time after operative treatment.

Multiple Sclerosis CSF Is Enriched With Follicular T Cells Displaying a Th1/Eomes Signature.

BACKGROUND AND OBJECTIVES: Tertiary lymphoid structures and aggregates are reported in the meninges of patients with multiple sclerosis (MS), especially at the progressive stage, and are strongly associated with cortical lesions and disability. Besides B cells, these structures comprise follicular helper T (Tfh) cells that are crucial to support B-cell differentiation. Tfh cells play a pivotal role in amplifying autoreactive B cells and promoting autoantibody production in several autoimmune diseases, but very few are known in MS. In this study, we examined the phenotype, frequency, and transcriptome of circulating cTfh cells in the blood and CSF of patients with relapsing-remitting MS (RRMS). METHODS: The phenotype and frequency of cTfh cells were analyzed in the blood of 39 healthy controls and 41 untreated patients with RRMS and in the CSF and paired blood of 10 patients with drug-naive RRMS at diagnosis by flow cytometry. Using an in vitro model of blood-brain barrier, we assessed the transendothelial migratory abilities of the different cTfh-cell subsets. Finally, we performed an RNA sequencing analysis of paired CSF cTfh cells and blood cTfh cells in 8 patients sampled at their first demyelinating event. RESULTS: The blood phenotype and frequency of cTfh cells were not significantly modified in patients with RRMS. In the CSF, we found an important infiltration of Tfh1 cells, with a high proportion of activated PD1+ cells. We demonstrated that the specific subset of Tfh1 cells presents increased migration abilities to cross an in vitro model of blood-brain barrier. Of interest, even at the first demyelinating event, cTfh cells in the CSF display specific characteristics with upregulation of EOMES gene and proinflammatory/cytotoxic transcriptomic signature able to efficiently distinguish cTfh cells from the CSF and blood. Finally, interactome analysis revealed potential strong cross talk between pathogenic B cells and CSF cTfh cells, pointing out the CSF as opportune supportive compartment and highlighting the very early implication of B-cell helper T cells in MS pathogenesis. DISCUSSION: Overall, CSF enrichment in activated Tfh1 as soon as disease diagnosis, associated with high expression of EOMES, and a predicted high propensity to interact with CSF B cells suggest that these cells probably contribute to disease onset and/or activity.

Cranial reconstruction evaluation - comparison of European statistical shape model performance on Chinese dataset.

Purpose: Morphological variability of the skull is an important consideration for cranioplasty and implant design. Differences in morphology of the skull based on the ethnicity are known. In a previous study we could show the accuracy and benefits of virtual reconstructions based on a statistical shape model (SSM) for neurocranial defects. As the SSM is trained on European data, the question arises how well this model fares when dealing with patients with a different ethnic background. In this study we aim to evaluate the accuracy and applicability of our proposed method when deploying a cranial SSM generated from European data to estimate missing parts of the neurocranium in a Chinese population. Methods: We used the same data and methods as in our previous study and compared the outcomes when applied to Chinese individuals. A large unilateral defect on the right side and a bilateral defect were created. The outer surface of the cranial table was reconstructed from CT scans, meshed with triangular elements, and registered to a template. Principal component analysis together with Thin Plate Spines (TPS) deformation was applied to quantify modes of variation. The mesh to mesh distances between the original defects´ surfaces and the reconstructed surface were computed. Results: Comparing the Chinese test group with the European control group, regarding the entire defect the analysis shows no significant difference for unilateral defects (test vs. control group/0.46 mm ± vs. 0.44 mm). Reconstruction of bilateral defects exhibited only in slightly higher prediction errors than those of unilateral defects (0.49 mm ± vs. 0.45 mm). Conclusion: The proposed method shows a high accuracy that seems to be ethnical independent - with low error margins for virtual skull reconstruction and implant design.Clinical relevance: Metallic objects may severely impact image quality in several CBCT devices.

Bridging 3D Slicer and ROS2 for Image-Guided Robotic Interventions.

Developing image-guided robotic systems requires access to flexible, open-source software. For image guidance, the open-source medical imaging platform 3D Slicer is one of the most adopted tools that can be used for research and prototyping. Similarly, for robotics, the open-source middleware suite robot operating system (ROS) is the standard development framework. In the past, there have been several "ad hoc" attempts made to bridge both tools; however, they are all reliant on middleware and custom interfaces. Additionally, none of these attempts have been successful in bridging access to the full suite of tools provided by ROS or 3D Slicer. Therefore, in this paper, we present the SlicerROS2 module, which was designed for the direct use of ROS2 packages and libraries within 3D Slicer. The module was developed to enable real-time visualization of robots, accommodate different robot configurations, and facilitate data transfer in both directions (between ROS and Slicer). We demonstrate the system on multiple robots with different configurations, evaluate the system performance and discuss an image-guided robotic intervention that can be prototyped with this module. This module can serve as a starting point for clinical system development that reduces the need for custom interfaces and time-intensive platform setup.

Reconstruction of dental roots for implant planning purposes: a feasibility study.

PURPOSE: Modern virtual implant planning is a time-consuming procedure, requiring a careful assessment of prosthetic and anatomical factors within a three-dimensional dataset. In order to facilitate the planning process and provide additional information, this study examines a statistical shape model (SSM) to compute the course of dental roots based on a surface scan. MATERIAL AND METHODS: Plaster models of orthognathic patients were scanned and superimposed with three-dimensional data of a cone-beam computer tomography (CBCT). Based on the open-source software "R", including the packages Morpho, mesheR, Rvcg and RvtkStatismo, an SSM was generated to estimate the tooth axes. The accuracy of the calculated tooth axes was determined using a leave-one-out cross-validation. The deviation of tooth axis prediction in terms of angle or horizontal shift is described with mean and standard deviation. The planning dataset of an implant surgery patient was additionally analyzed using the SSM. RESULTS: 71 datasets were included in this study. The mean angle between the estimated tooth-axis and the actual tooth-axis was 7.5 ± 4.3° in the upper jaw and 6.7 ± 3.8° in the lower jaw. The horizontal deviation between the tooth axis and estimated axis was 1.3 ± 0.8 mm close to the cementoenamel junction, and 0.7 ± 0.5 mm in the apical third of the root. Results for models with one missing tooth did not differ significantly. In the clinical dataset, the SSM could give a reasonable aid for implant positioning. CONCLUSIONS: With the presented SSM, the approximate course of dental roots can be predicted based on a surface scan. There was no difference in predicting the tooth axis of existent or missing teeth. In clinical context, the estimation of tooth axes of missing teeth could serve as a reference for implant positioning. However, a higher number of training data must be achieved to obtain increasing accuracy.

Automated segmentation of head CT scans for computer-assisted craniomaxillofacial surgery applying a hierarchical patch-based stack of convolutional neural networks.

PURPOSE: Computer-assisted techniques play an important role in craniomaxillofacial surgery. As segmentation of three-dimensional medical imaging represents a cornerstone for these procedures, the present study was aiming at investigating a deep learning approach for automated segmentation of head CT scans. METHODS: The deep learning approach of this study was based on the patchwork toolbox, using a multiscale stack of 3D convolutional neural networks. The images were split into nested patches using a fixed 3D matrix size with decreasing physical size in a pyramid format of four scale depths. Manual segmentation of 18 craniomaxillofacial structures was performed in 20 CT scans, of which 15 were used for the training of the deep learning network and five were used for validation of the results of automated segmentation. Segmentation accuracy was evaluated by Dice similarity coefficient (DSC), surface DSC, 95% Hausdorff distance (95HD) and average symmetric surface distance (ASSD). RESULTS: Mean for DSC was 0.81 ± 0.13 (range: 0.61 [mental foramen] - 0.98 [mandible]). Mean Surface DSC was 0.94 ± 0.06 (range: 0.87 [mental foramen] - 0.99 [mandible]), with values > 0.9 for all structures but the mental foramen. Mean 95HD was 1.93 ± 2.05 mm (range: 1.00 [mandible] - 4.12 mm [maxillary sinus]) and for ASSD, a mean of 0.42 ± 0.44 mm (range: 0.09 [mandible] - 1.19 mm [mental foramen]) was found, with values < 1 mm for all structures but the mental foramen. CONCLUSION: In this study, high accuracy of automated segmentation of a variety of craniomaxillofacial structures could be demonstrated, suggesting this approach to be suitable for the incorporation into a computer-assisted craniomaxillofacial surgery workflow. The small amount of training data required and the flexibility of an open source-based network architecture enable a broad variety of clinical and research applications.

A Novel Method for Digital Reconstruction of the Mucogingival Borderline in Optical Scans of Dental Plaster Casts.

Adequate soft-tissue dimensions have been shown to be crucial for the long-term success of dental implants. To date, there is evidence that placement of dental implants should only be conducted in an area covered with attached gingiva. Modern implant planning software does not visualize soft-tissue dimensions. This study aims to calculate the course of the mucogingival borderline (MG-BL) using statistical shape models (SSM). Visualization of the MG-BL allows the practitioner to consider the soft tissue supply during implant planning. To deploy an SSM of the MG-BL, healthy individuals were examined and the intra-oral anatomy was captured using an intra-oral scanner (IOS). The empirical anatomical data was superimposed and analyzed by principal component analysis. Using a Leave-One-Out Cross Validation (LOOCV), the prediction of the SSM was compared with the original anatomy extracted from IOS. The median error for MG-BL reconstruction was 1.06 mm (0.49-2.15 mm) and 0.81 mm (0.38-1.54 mm) for the maxilla and mandible, respectively. While this method forgoes any technical work or additional patient examination, it represents an effective and digital method for the depiction of soft-tissue dimensions. To achieve clinical applicability, a higher number of datasets has to be implemented in the SSM.

CD40L-expressing CD4+ T cells prime adipose-derived stromal cells to produce inflammatory chemokines.

The therapeutic potential of culture-adapted adipose-derived stromal cells (ASCs) is largely related to their production of immunosuppressive factors that are inducible in vitro by priming with inflammatory stimuli, in particular tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). In vivo, obesity is associated with chronic inflammation of white adipose tissue, including accumulation of neutrophils, infiltration by IFNγ/TNFα-producing immune cells, and ASC dysfunction. In the current study, we identified in obese patients a simultaneous upregulation of CD40Lin the adipose tissue stroma vascular fraction (AT-SVF), correlated with the Th1 gene signature, and an overexpression of CD40 by native ASCs. Moreover, activated CD4+ T cells upregulated CD40 on culture-expanded ASCs and triggered their production of IL-8 in a CD40L-dependent manner, leading to an increased capacity to recruit neutrophils. Finally, activation of ASCs by sCD40L or CD40L-expressing CD4+ T cells relies on both canonical and non-canonical NF-κB pathways, and IL-8 was found to be coregulated with NF-κB family members in AT-SVF. These data identify the CD40-CD40L axis as a priming mechanism of ASCs, able to modulate their cross talk with neutrophils in an inflammatory context, and their functional capacity for therapeutic applications.