Follicular lymphoma triggers phenotypic and functional remodeling of the human lymphoid stromal cell landscape.

Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing, and functional assays, defining three distinct human LSC subsets. The integrin CD49a designated perivascular stromal cells exhibiting features of local committed LSC precursors and segregated cytokine and chemokine-producing fibroblastic reticular cells (FRCs) supporting B and T cell survival. The follicular dendritic cell transcriptional profile reflected active responses to B cell and non-B cell stimuli. We therefore examined the effect of B cell stimuli on LSCs in follicular lymphoma (FL). FL B cells interacted primarily with CD49a+ FRCs. Transcriptional analyses revealed LSC reprogramming in situ downstream of the cytokines tumor necrosis factor (TNF) and transforming growth factor ß (TGF-ß), including increased expression of the chemokines CCL19 and CCL21. Our findings define human LSC populations in healthy tissue and reveal bidirectional crosstalk between LSCs and malignant B cells that may present a targetable axis in lymphoma.

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.

Extracellular vesicles shed by follicular lymphoma B cells promote polarization of the bone marrow stromal cell niche.

Follicular lymphoma (FL) originates in the lymph nodes (LNs) and infiltrates bone marrow (BM) early in the course of the disease. BM FL B cells are characterized by a lower cytological grade, decreased proliferation, and a specific phenotypic and subclonal profile. Mesenchymal stromal cells (MSCs) obtained from FL BM display a specific gene expression profile (GEP), including enrichment for a lymphoid stromal cell signature, and an increased capacity to sustain FL B-cell growth. However, the mechanisms triggering the formation of the medullar FL permissive stromal niche have not been identified. In the current work, we demonstrate that FL B cells produce extracellular vesicles (EVs) that can be internalized by BM-MSCs, making them more efficient to support FL B-cell survival and quiescence. Accordingly, EVs purified from FL BM plasma activate transforming growth factor ß-dependent and independent pathways in BM-MSCs and modify their GEP, triggering an upregulation of factors classically associated with hematopoietic stem cell niche, including CXCL12 and angiopoietin-1. Moreover, we provide the first characterization of BM FL B-cell GEP, allowing the definition of the landscape of molecular interactions they could engage with EV-primed BM-MSCs. This work identifies FL-derived EVs as putative mediators of BM stroma polarization and supports further investigation of their clinical interest for targeting the crosstalk between BM-MSCs and malignant B cells.

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.

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.

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.

Measuring standing hindfoot alignment: reliability of different approaches in conventional x-ray and cone-beam CT.

INTRODUCTION: Currently there is no consensus how hindfoot alignment (HA) should be assessed in CBCT scans. The aim of this study is to investigate how the reliability is affected by the anatomical structures chosen for the measurement. MATERIALS AND METHODS: Datasets consisting of a Saltzman View (SV) and a CBCT of the same foot were acquired prospectively and independently assessed by five raters regarding HA. In SVs the HA was estimated as follows: transversal shift between tibial shaft axis and heel contact point (1); angle between tibial shaft axis and a tangent at the medial (2) or lateral (3) calcaneal wall. In CBCT the HA was estimated as follows: transversal shift between the centre of the talus and the heel contact point (4); angle between a perpendicular line and a tangent at the medial (5) or lateral (6) calcaneal wall; angle between the distal tibial surface and a tangent at the medial calcaneal wall (7). Intraclass correlation coefficients (ICC) were calculated to assess inter-rater reliability. A linear regression was performed to compare the different measurement regarding their correlation. RESULTS: 32 patients were included in the study. The ICCs for the measurements 1-7 were as follows: (1) 0.924 [95% CI 0.876-0.959] (2) 0.533 [95% CI 0.377-0.692], (3) 0.553 [95% CI 0.399-0.708], (4) 0.930 [95% CI 0.866-0.962], (5) 0.00 [95% CI - 0.111 to 0.096], (6) 0.00 [95% CI - 0.103 to 0.111], (7) 0.152 [95% CI 0.027-0.330]. A linear regression between measurement 1 and 4 showed a correlation of 0.272 (p = 0.036). CONCLUSIONS: It could be shown that reliability of measuring HA depends on the investigated anatomical structure. Placing a tangent along the calcaneus (2, 3, 5, 6, 7) was shown to be unreliable, whereas determining the weight-bearing heel point (1, 4) appeared to be a reliable approach. The correlation of the measurement workflows is significant (p = 0.036), but too weak (0.272) to be used clinically.

Creating an anatomical wax-up in partially edentulous patients by means of a statistical shape model.

PURPOSE: Creating wax-ups of missing teeth for backward planning in implant surgery is a complex and time-consuming process. To facilitate implant-planning procedures, the automatic generation of a virtual wax-up would be useful. In the present study, the reconstruction of missing teeth in partially edentulous patients was performed automatically using newly developed software. The accuracy was investigated in order to test its clinical applicability. MATERIALS AND METHODS: This study presents a new method for creating an automatic virtual wax-up, which could serve as a basic tool in modern implant-planning procedures. First, a statistical shape model (SSM) based on 76 maxillary and mandibular arch scans from dentally healthy individuals was generated. Then, artificially generated tooth gaps were reconstructed. The accuracy of the workflow was evaluated on a separate testing sample of 10 individuals with artificially created tooth gaps given as a median deviation, in millimeters. Scans of three clinical cases with partial edentulism were equally reconstructed using the SSM and compared with the final prosthodontic work. RESULTS: The reconstruction of the artificial tooth gaps could be performed with the following median reconstruction accuracy: gap 21 with 0.15 mm; gap 27 with 0.20 mm; gap 34 with 0.22 mm: gap 36 with 0.22 mm; gaps 12 to 22 with 0.22 mm; gaps 34 to 36 with 0.22 mm. A scenario for an almost edentulous mandible with all teeth missing except teeth 33 and 43 could be reconstructed with a median reconstruction accuracy of 0.37 mm. The median tooth gap deviation of the SSM-based reconstruction in clinical cases differed from the final inserted prosthodontic teeth by 0.49 to 0.86 mm in median. CONCLUSION: A first feasibility of creating virtual wax-ups using an SSM could be shown. Artificially generated tooth gaps could be reconstructed close to the original with the proposed workflow. In the clinical cases, the SSM proposes an anatomical reconstruction, which does not yet consider prosthodontic aspects. To obtain clinical use, contact with antagonist teeth must be considered and more training data must be implemented. However, the presented method offers a fast and viable way for the approximate placement of missing crowns. This could be used in a digital planning workflow when implant position must be determined. (Int J Comput Dent 2022;25(4):349-0; doi: 10.3290/j.ijcd.b2599407).

APERO: a genome-wide approach for identifying bacterial small RNAs from RNA-Seq data.

Small non-coding RNAs (sRNAs) regulate numerous cellular processes in all domains of life. Several approaches have been developed to identify them from RNA-seq data, which are efficient for eukaryotic sRNAs but remain inaccurate for the longer and highly structured bacterial sRNAs. We present APERO, a new algorithm to detect small transcripts from paired-end bacterial RNA-seq data. In contrast to previous approaches that start from the read coverage distribution, APERO analyzes boundaries of individual sequenced fragments to infer the 5' and 3' ends of all transcripts. Since sRNAs are about the same size as individual fragments (50-350 nucleotides), this algorithm provides a significantly higher accuracy and robustness, e.g., with respect to spontaneous internal breaking sites. To demonstrate this improvement, we develop a comparative assessment on datasets from Escherichia coli and Salmonella enterica, based on experimentally validated sRNAs. We also identify the small transcript repertoire of Dickeya dadantii including putative intergenic RNAs, 5' UTR or 3' UTR-derived RNA products and antisense RNAs. Comparisons to annotations as well as RACE-PCR experimental data confirm the precision of the detected transcripts. Altogether, APERO outperforms all existing methods in terms of sRNA detection and boundary precision, which is crucial for comprehensive genome annotations. It is freely available as an open source R package on https://github.com/Simon-Leonard/APERO.

Do Red Blood Cell Transfusions Influence Long-Term Outcomes in Patients Undergoing Primary Surgery for Oral Squamous Cell Carcinoma?

PURPOSE: There is no consensus on the impact of red blood cell (RBC) transfusion on patients with oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the association between RBC transfusions and overall survival (OS) and tumor-free survival (TFS) after operative treatment of OSCC. METHODS: In this retrospective cohort study, all patients treated with primary surgery between 2003 and 2017 because of OSCC were chart reviewed. The occurrence and amount of RBC transfusions (0; 1-3; >3 units) was correlated with OS and TFS by Kaplan-Meier survival and Cox regression analyses. Demographic, clinical, and pathological parameters were also evaluated in order to identify confounding factors. RESULTS: Of 420 patients (243 [57.9%] male) with a mean age of 62.6 years, 67 (16.0%) received RBC transfusion. There were statistically significant (P < .01) differences in 5-year OS respectively TFS in transfused patients for the Kaplan-Meier survival analysis (0 units = 70.6%; [95% confidence interval {CI}: 65.0-75.4%] respectively 63.2% [95% CI: 57.4-68.4%], 1-3 units = 47.2% [95% CI: 29.4-63.1%] respectively 40.6% [95% CI: 24.6-55.95%] and >3 units = 48.9% [95% CI: 20.9-72.1%] respectively 30.5% [95% CI: 8.9-55.8%]). After multivariate adjustments for demographic, clinical, and pathological parameters, RBC transfusion could not be sustained as a significant prognostic factor in OS respectively TFS (1-3 units: hazard ratio = 1.5 [95% CI: 0.7-3.2] respectively 1.3 [95% CI: 0.7-2.6]; >3 units: hazard ratio = 1.2 [95% CI: 0.5 - 3.0] respectively 1.1 [95% CI: 0.5-2.4]). CONCLUSIONS: Although RBC transfusion was not identified as a significant prognostic parameter in multivariate analysis, a clear trend for shorter OS and TFS for transfused patients in univariate and Kaplan-Meier survival analysis could be shown.

Successful Management of Cleft Lip and Palate Malformation without Pre-Surgical Infant Orthopedics.

OBJECTIVE: To investigate the effect of lip closure on reduction of cleft palates when no pre-surgical infant orthopedics (PSIO) are used. STUDY DESIGN: Retrospective patient chart-review in our department for Cranio-Maxillofacial Surgery at the University Medical Centre Freiburg, Germany. 19 patients at the age of 5.9 ± 2.1 months with surgical treatment of uni- (UCLP), or bilateral cleft lip and palate (BCLP) without any use of PSIO were included. RESULTS: Early soft tissue correction of the lip leads to an effective reduction of the maxillary arch without any use of PSIO. The presented conventional and digital measurements appeared to be reliable. A successful reduction of the cleft width (UCLP = 3.88 ± 2.42mm, BCLP = 7.33 ± 5.00mm), the width of the alveolar arch (1.91 ± 1.36mm) and the sagittal depth of the alveolar arch (3.07 ± 2.71 mm) could be achieved with the presented workflow. CONCLUSIONS: Cleft reduction was obtainable without PSIO when lip closure after Tennison-Randall was performed.

The phytopathogenic nature of Dickeya aquatica 174/2 and the dynamic early evolution of Dickeya pathogenicity.

Dickeya is a genus of phytopathogenic enterobacterales causing soft rot in a variety of plants (e.g. potato, chicory, maize). Among the species affiliated to this genus, Dickeya aquatica, described in 2014, remained particularly mysterious because it had no known host. Furthermore, while D. aquatica was proposed to represent a deep-branching species among Dickeya genus, its precise phylogenetic position remained elusive. Here, we report the complete genome sequence of the D. aquatica type strain 174/2. We demonstrate the affinity of D. aquatica strain 174/2 for acidic fruits such as tomato and cucumber and show that exposure of this bacterium to acidic pH induces twitching motility. An in-depth phylogenomic analysis of all available Dickeya proteomes pinpoints D. aquatica as the second deepest branching lineage within this genus and reclassifies two lineages that likely correspond to new genomospecies (gs.): Dickeya gs. poaceaephila (Dickeya sp NCPPB 569) and Dickeya gs. undicola (Dickeya sp 2B12), together with a new putative genus, tentatively named Prodigiosinella. Finally, from comparative analyses of Dickeya proteomes, we infer the complex evolutionary history of this genus, paving the way to study the adaptive patterns and processes of Dickeya to different environmental niches and hosts. In particular, we hypothesize that the lack of xylanases and xylose degradation pathways in D. aquatica could reflect adaptation to aquatic charophyte hosts which, in contrast to land plants, do not contain xyloglucans.

Plant-phytopathogen interactions: bacterial responses to environmental and plant stimuli.

Plant pathogenic bacteria attack numerous agricultural crops, causing devastating effects on plant productivity and yield. They survive in diverse environments, both in plants, as pathogens, and also outside their hosts as saprophytes. Hence, they are confronted with numerous changing environmental parameters. During infection, plant pathogens have to deal with stressful conditions, such as acidic, oxidative and osmotic stresses; anaerobiosis; plant defenses; and contact with antimicrobial compounds. These adverse conditions can reduce bacterial survival and compromise disease initiation and propagation. Successful bacterial plant pathogens must detect potential hosts and also coordinate their possibly conflicting programs for survival and virulence. Consequently, these bacteria have a strong and finely tuned capacity for sensing and responding to environmental and plant stimuli. This review summarizes our current knowledge of the signals and genetic circuits that affect survival and virulence factor expression in three important and well-studied plant pathogenic bacteria with wide host ranges and the capacity for long-term environmental survival. These are: Ralstonia solanacerarum, a vascular pathogen that causes wilt disease; Agrobacterium tumefaciens, a biotrophic tumorigenic pathogen responsible for crown gall disease and Dickeya, a brute force apoplastic pathogen responsible for soft-rot disease.

Kinect technology for hand tracking control of surgical robots: technical and surgical skill comparison to current robotic masters.

BACKGROUND: Current surgical robots are controlled by a mechanical master located away from the patient, tracking surgeon's hands by wire and pulleys or mechanical linkage. Contactless hand tracking for surgical robot control is an attractive alternative, because it can be executed with minimal footprint at the patient's bedside without impairing sterility, while eliminating current disassociation between surgeon and patient. We compared technical and technologic feasibility of contactless hand tracking to the current clinical standard master controllers. METHODS: A hand-tracking system (Kinect™-based 3Gear), a wire-based mechanical master (Mantis Duo), and a clinical mechanical linkage master (da Vinci) were evaluated for technical parameters with strong clinical relevance: system latency, static noise, robot slave tremor, and controller range. Five experienced surgeons performed a skill comparison study, evaluating the three different master controllers for efficiency and accuracy in peg transfer and pointing tasks. RESULTS: da Vinci had the lowest latency of 89 ms, followed by Mantis with 374 ms and 3Gear with 576 ms. Mantis and da Vinci produced zero static error. 3Gear produced average static error of 0.49 mm. The tremor of the robot used by the 3Gear and Mantis system had a radius of 1.7 mm compared with 0.5 mm for da Vinci. The three master controllers all had similar range. The surgeons took 1.98 times longer to complete the peg transfer task with the 3Gear system compared with Mantis, and 2.72 times longer with Mantis compared with da Vinci (p value 2.1e-9). For the pointer task, surgeons were most accurate with da Vinci with average error of 0.72 mm compared with Mantis's 1.61 mm and 3Gear's 2.41 mm (p value 0.00078). CONCLUSIONS: Contactless hand-tracking technology as a surgical master can execute simple surgical tasks. Whereas traditional master controllers outperformed, given that contactless hand-tracking is a first-generation technology, clinical potential is promising and could become a reality with some technical improvements.

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.

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.

The new species Enterobacter oryziphilus sp. nov. and Enterobacter oryzendophyticus sp. nov. are key inhabitants of the endosphere of rice.

BACKGROUND: Six independent Gram-negative, facultatively anaerobic, non-spore-forming, nitrogen-fixing rod-shaped isolates were obtained from the root endosphere of rice grown at the International Rice Research Institute (IRRI) and investigated in a polyphasic taxonomic study. RESULTS: The strains produced fatty acid patterns typical for members of the family Enterobacteriaceae. Comparative sequence analyses of the 16S rRNA as well as rpoB genes allocated the strains to two well-defined groups within the genus Enterobacter, family Enterobacteriaceae. The analyses indicated Enterobacter radicincitans, Enterobacter arachidis and Enterobacter oryzae to be the closest related species. An RpoB (translated) protein comparison supported the placement in the genus Enterobacter and the relatedness of our isolates to the aforementioned species. Genomic DNA:DNA hybridization analyses and biochemical analyses provided further evidence that the novel strains belong to two new species within the genus Enterobacter. The two species can be differentiated from each other and from existing enteric species by acid production from L-rhamnose and D-melibiose, decarboxylation of ornithine and utilization of D-alanine, D-raffinose L-proline and L-aspartic acid, among other characteristics. Members of both species revealed capacities to colonise rice roots, including plant-growth-promoting capabilities such as an active supply of fixed nitrogen to the plant and solubilisation of inorganic phosphorus, next to traits allowing adaptation to the plant. CONCLUSIONS: Two novel proposed enterobacterial species, denominated Enterobacter oryziphilus sp. nov. (type strain REICA_142(T)=LMG 26429(T)=NCCB 100393(T)) and Enterobacter oryzendophyticus sp. nov. (type strain REICA_082(T)=LMG 26432(T) =NCCB 100390(T)) were isolated from rice roots. Both species are capable of promoting rice growth by supplying nitrogen and phosphorus.