Cancer-associated fibroblasts in the tumor microenvironment of tongue carcinoma is a heterogeneous cell population

Objectives: To examine different immunophenotypes of cancer-associated fibroblasts (CAFs) in tongue squamous cell carcinoma (TSCC) and to investigate how they related to clinical outcomes. Methods: Serial sections from 54 cases of TSCC were immunohistochemically stained with a-smooth muscle actin (alpha SMA, CAF marker) to determine CAF density, and double-immunostained with alpha SMA combined with CD80 and CD86 (myeloid/monocytic-derived cell markers), Nanog (mesenchymal stem cell marker) and CD133 (hematopoietic/endothelial stem cell marker). Density of cells co-expressing these marker combinations was semi-quantitatively assessed in 5 randomly selected high power fields within the tumor area and scored as 1 - one-to-five stained cells in each field, 2 - more than 5 stained cells in each field; any finding less than score 1, was allocated a score of 0. Results: There were 26 CAF-poor, 16 CAF-rich and 12 CAF-intermediated cases. CD86(+) alpha SMA(+) cells were the most frequent (80.4%) followed by CD80(+) alpha SMA(+) (72%) and Nanog(+) alpha SMA(+) cells (56%). The CD133(+) alpha SMA(+) phenotype was found only in association with blood vessels. High density of aSMA CAFs was associated with disease recurrence and poor survival (p <0.05). Increased density of CD86(+) alpha SMA(+) cells was significantly associated with CAF-rich tumors and with poor survival (p <0.05). Conclusion: In TSCC, CAFs demonstrate heterogeneous and overlapping phenotypes with the myeloid/monocytic type being the most frequent and having an impact on the clinical outcomes. Further studies are needed in order to further characterize CAF phenotypes in carcinomas of various oral sites, as this may open new frontiers for personalized medicine.Peer reviewe

Markers of the pre-metastatic niche "knock on the door" of metastasis-free cervical lymph nodes in patients with oral cancer

Aim: To assess expression of some markers of the pre-metastatic niche (PMN) in lymph nodes (LNs) of oral cancer patients. Materials: LNs from metastatic-free neck dissections (LN0/N0, N = 43) and metastatic-free LNs in the vicinity of metastasis-containing LNs (LN0/N+, N = 30) were immuno-histochemically stained for lysyl oxidase (LOX), fibronectin (FN), vascular-endothelial growth factor receptor (VEGFR)-1 and matrix metalloproteinase (MMP)-9. Staining was assessed as 0 (no or weak staining), 1 (strong stain in 25% cells or extracellular area), 2 (same as 1 but in up to 50%) and 3 (same as 1 but in > than 50% of cells/area). Assessment was performed in the lymph node capsule (CAP), sub-capsular sinus (SCS) and medullary sinus (MS). In addition, sections were stained with picrosirius red and examined with polarized microscopy for assessing the distribution of polarization colors of the collagen fibers in the LN capsular area. Results: All examined LNs were positive for markers of the PMN. In general, the distribution and intensity of the immunoreactivity was similar between the LN0/N0 and LN0/N +, with only a few differences regarding expression of LOX in the capsule (p = 0.002) and VEGFR1 and MMP9 in the SCS (p = 0.023 and p <0.001, respectively). Picrosirius red stain and polarized microscopy revealed a disrupted arrangement and distribution of the collagen fibers in both LN0/N0 and LN0/N +. Conclusion: Markers for PMN were shown for the first time to be expressed in cervical LN0/N0 from patients with oral cancer, suggesting the increased permissive pathway remotely paved by the primary oral tumor for the incoming metastatic cells.Peer reviewe

Identifying Knots of Trust in Virtual Communities

Part 2: Full PapersInternational audienceKnots of trust are groups of community members having overall “strong” trust relations between them. In previous work we introduced the knot aware trust based reputation model. According to this model, in order to provide a member with reputation information relative to her viewpoint, the system must identify the knot to which that member belongs and interpret its reputation data correctly. In the current paper we present the problem of identifying knots which is modeled as a graph clustering problem, where vertices correspond to individuals and edges describe trust relationships between them. We propose a new perspective for clustering that reflects the subjective idea of trust and the nature of the community. A class of weight functions is suggested for assigning edge weights and their impact on the stability and strength of knots is demonstrated. Finally we show the efficiency of knots of high quality for providing their members with relevant reputation information

Datasets of RT spoofing attacks on MIL-STD-1553 communication traffic

The datasets in this article are produced to evaluate the ability of MIL-STD-1553 intrusion detection systems to detect attacks that emulate normal non-periodical messages, at differing attack occurrence rates. And different data representations. We present three streams of simulated MIL-STD-1553 traffic containing both normal and attack messages corresponding to packets that were injected into the bus by a malicious remote terminal. The implemented attacks emulate normal non-periodical communication so detecting them with a low false positive rate is non-trivial. Each stream is separated into a training set of normal messages and a test set of both normal and attack messages. The test sets differ by the occurrence rate of attack messages (0.01%, 0.10%, and 1.00%). Each stream is also preprocessed into a dataset of message sequences so that it can be used for sequential anomaly detection analysis. The sequential test sets differ by the occurrence rate of attack sequences (0.14%, 1.26%, and 11.01%). All dataset files can be found in Mendeley Data, doi:10.17632/jvgdrmjvs3.3

Upper jugular lymph nodes (submuscular recess) in non-squamous-cell cancer of the head and neck: surgical considerations

Cervical lymphadenectomy of level II encompasses lymph nodes associated with the upper internal jugular vein and the spinal accessory nerve (SAN). Removal of tissue superior to the SAN (submuscular recess-(SMR)) was recently shown to be unwarranted in selected cases of squamous-cell cancer. Thirtyfive patients with non-squamous-cell cancer (SCC) of the head and neck treated with cervical lymphadenectomy were prospectively evaluated. Thirty-seven neck dissection specimens were histologically analysed for the number of lymph nodes involved with cancer. At the time of surgery, level II was separated into the supraspinal accessory nerve component (IIa) and the component anterior to the SAN (IIb). Neck dissections were most commonly performed for cancer of the thyroid gland (19) followed in frequency by the parotid gland (seven), skin: melanoma (five), basal-cell cancer (two), and other sites (four). Twenty-five neck dissections were modified-selective procedures and 12 were either radical or modified radical neck dissection. Twenty-nine necks were clinically N+ and eight N0. Histological staging was pathologically N+ in 32 neck dissection specimens. Level IIb contained an average of 12 nodes and the IIa component contained a mean of 5.0 nodes. Level II contained metastatic disease in 28 of 32 histologically node-positive specimens (87 per cent). Level IIa was involved with cancer in six cases (16 per cent), five of which were pre-operatively staged as clinically N+. All cases (100 per cent) with level IIa involvement had level IIb positive nodes. Three of the level IIa positive cases were cancer of the parotid gland comprising 43 per cent of this sub-group of patients. Incidence of involvement of SMR in non-SCC cases is not uncommon. The additional time required and morbidity associated with dissection of the supraspinal accessory nerve component of level II are probably justified when performing neck dissection in cancer of the thyroid gland. The SMR should be excised in cancer of the parotid gland. Large-scale prospective controlled studies with long-term follow-up periods are necessary to support resection of level IIb only

Impact and Stability of Mandibular Setback after Intraoral Vertical Ramus Osteotomy

(1) Background: The purpose of this study was to evaluate stability and complications following mandibular setback using intraoral vertical ramus osteotomy (IVRO) and provide an assessment of IMF (Inter-maxillary Fixation) compliance. (2) Methods: This is a retrospective cohort study. It included a total of 39 patients who underwent 78 IVRO for the treatment of mandibular prognathism between 2005 and 2021 at Sheba Medical Center. Radiographic and clinical examinations were performed preoperatively (T0), 3 days post-surgery (T1) and 8 months post-surgery (T2). Measurements of dental and skeletal stability, as well as neurosensory disturbances and TMJ dysfunctions, were statistically analyzed. (3) Results: The mean mandibular setback was 5.6 mm. A relapse of less than 2 mm was observed at T2. A short-term neurological disturbance was reported in 38.46% of the 39 patients, and 17.94% of them showed full recovery by T2. In 21 patients who underwent IVRO without genioplasty, only 14.28% reported long-term sensory disturbance. In addition, when a vertical osteotomy was performed, neurological damage was 174% higher as compared to oblique osteotomy. The IMF compliance rate for the 6 weeks postoperatively was 100%. (4) Conclusions: IVRO is still a relevant and valid technique for the treatment of mandibular prognathism that provides stable results with minimal complications rate

Impact and Stability of Mandibular Setback after Intraoral Vertical Ramus Osteotomy

(1) Background: The purpose of this study was to evaluate stability and complications following mandibular setback using intraoral vertical ramus osteotomy (IVRO) and provide an assessment of IMF (Inter-maxillary Fixation) compliance. (2) Methods: This is a retrospective cohort study. It included a total of 39 patients who underwent 78 IVRO for the treatment of mandibular prognathism between 2005 and 2021 at Sheba Medical Center. Radiographic and clinical examinations were performed preoperatively (T0), 3 days post-surgery (T1) and 8 months post-surgery (T2). Measurements of dental and skeletal stability, as well as neurosensory disturbances and TMJ dysfunctions, were statistically analyzed. (3) Results: The mean mandibular setback was 5.6 mm. A relapse of less than 2 mm was observed at T2. A short-term neurological disturbance was reported in 38.46% of the 39 patients, and 17.94% of them showed full recovery by T2. In 21 patients who underwent IVRO without genioplasty, only 14.28% reported long-term sensory disturbance. In addition, when a vertical osteotomy was performed, neurological damage was 174% higher as compared to oblique osteotomy. The IMF compliance rate for the 6 weeks postoperatively was 100%. (4) Conclusions: IVRO is still a relevant and valid technique for the treatment of mandibular prognathism that provides stable results with minimal complications rate