Raman difference spectroscopy and U-Net convolutional neural network for molecular analysis of cutaneous neurofibroma.

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins-complete tumor removal while attempting to preserve viable tissue-remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

Layer-by-Layer Deposition of Regenerated Silk Fibroin─An Approach to the Surface Coating of Biomedical Implant Materials.

Biomaterials and coating techniques unlock major benefits for advanced medical therapies. Here, we explored layer-by-layer (LbL) deposition of silk fibroin (SF) by dip coating to deploy homogeneous films on different materials (titanium, magnesium, and polymers) frequently used for orthopedic and other bone-related implants. Titanium and magnesium specimens underwent preceding plasma electrolytic oxidation (PEO) to increase hydrophilicity. This was determined as surface properties were visualized by scanning electron microscopy and contact angle measurements as well as Fourier transform infrared spectroscopy (FTIR) analysis. Finally, biological in vitro evaluations of hemocompatibility, THP-1 cell culture, and TNF-α assays were conducted. A more hydrophilic surface could be achieved using the PEO surface, and the contact angle for magnesium and titanium showed a reduction from 73 to 18° and from 58 to 17°, respectively. Coating with SF proved successful on all three surfaces, and coating thicknesses of up to 5.14 µm (±SD 0.22 µm) were achieved. Using FTIR analysis, it was shown that the insolubility of the material was achieved by post-treatment with water vapor annealing, although the random coil peak (1640-1649 cm-1) and the α-helix peak (at 1650 cm-1) were still evident. SF did not change hemocompatibility, regardless of the substrate, whereas the PEO-coated materials showed improved hemocompatibility. THP-1 cell culture showed that cells adhered excellently to all of the tested material surfaces. Interestingly, SF coatings induced a significantly higher amount of TNF-α for all materials, indicating an inflammatory response, which plays an important role in a variety of physiological processes, including osteogenesis. LbL coatings of SF are shown to be promising candidates to modulate the body's immune response to implants manufactured from titanium, magnesium, and polymers. They may therefore facilitate future applications for bioactive implant coatings. However, further in vivo studies are needed to confirm the proposed effects on osteogenesis in a physiological environment.

Raman spectroscopy and U-Net deep neural network in antiresorptive drug-related osteonecrosis of the jaw.

OBJECTIVE: Application of an optical method for the identification of antiresorptive drug-related osteonecrosis of the jaw (ARONJ). METHODS: We introduce shifted-excitation Raman difference spectroscopy followed by U-Net deep neural network refinement to determine bone tissue viability. The obtained results are validated through established histological methods. RESULTS: Discrimination of osteonecrosis from physiological tissues was evaluated at 119 distinct measurement loci in 40 surgical specimens from 28 patients. Mean Raman spectra were refined from 11,900 raw spectra, and characteristic peaks were assigned to their respective molecular origin. Then, following principal component and linear discriminant analyses, osteonecrotic lesions were distinguished from physiological tissue entities, such as viable bone, with a sensitivity, specificity, and overall accuracy of 100%. Moreover, bone mineral content, quality, maturity, and crystallinity were quantified, revealing an increased mineral-to-matrix ratio and decreased carbonate-to-phosphate ratio in ARONJ lesions compared to physiological bone. CONCLUSION: The results demonstrate feasibility with high classification accuracy in this collective. The differentiation was determined by the spectral features of the organic and mineral composition of bone. This merely optical, noninvasive technique is a promising candidate to ameliorate both the diagnosis and treatment of ARONJ in the future.

Effects of Infantile Hypophosphatasia on Human Dental Tissue.

Hypophosphatasia (HPP) is an inherited, systemic disorder, caused by loss-of-function variants of the ALPL gene encoding the enzyme tissue non-specific alkaline phosphatase (TNSALP). HPP is characterized by low serum TNSALP concentrations associated with defective bone mineralization and increased fracture risk. Dental manifestations have been reported as the exclusive feature (odontohypophosphatasia) and in combination with skeletal complications. Enzyme replacement therapy (asfotase alfa) has been shown to improve respiratory insufficiency and skeletal complications in HPP patients, while its effects on dental status have been understudied to date. In this study, quantitative backscattered electron imaging (qBEI) and histological analysis were performed on teeth from two patients with infantile HPP before and during asfotase alfa treatment and compared to matched healthy control teeth. qBEI and histological methods revealed varying mineralization patterns in cementum and dentin with lower mineralization in HPP. Furthermore, a significantly higher repair cementum thickness was observed in HPP compared to control teeth. Comparison before and during treatment showed minor improvements in mineralization and histological parameters in the patient when normalized to matched control teeth. HPP induces heterogeneous effects on mineralization and morphology of the dental status. Short treatment with asfotase alfa slightly affects mineralization in cementum and dentin. Despite HPP being a rare disease, its mild form occurs at higher prevalence. This study is of high clinical relevance as it expands our knowledge of HPP and dental involvement. Furthermore, it contributes to the understanding of dental tissue treatment, which has hardly been studied so far.

Horizontal augmentation techniques in the mandible: a systematic review.

PURPOSE: Placement of dental implants has evolved to be an advantageous treatment option for rehabilitation of the fully or partially edentulous mandible. In case of extensive horizontal bone resorption, the bone volume needs to be augmented prior to or during implant placement in order to obtain dental rehabilitation and maximize implant survival and success. METHODS: Our aim was to systematically review the available data on lateral augmentation techniques in the horizontally compromised mandible considering all grafting protocols using xenogeneic, synthetic, or allogeneic material. A computerized and manual literature search was performed for clinical studies (published January 1995 to March 2021). RESULTS: Eight studies ultimately met the inclusion criteria comprising a total of 276 procedures of xenogeneic, allogeneic, or autogenous bone graft applications in horizontal ridge defects. Particulate materials as well as bone blocks were used as grafts with a mean follow-up of 26.0 months across all included studies. Outcome measures, approaches and materials varied from study to study. A gain of horizontal bone width of the mandible with a mean of 4.8 mm was observed in seven of eight studies. All but one study, reported low bone graft failure rates of 4.4% in average. CONCLUSIONS: Only limited data are available on the impact of different horizontal augmentation strategies in the mandible. The results show outcomes for xenogeneic as well as autologous bone materials for horizontal ridge augmentation of the lower jaw. The use of allogeneic bone-block grafts in combination with resorbable barrier membranes must be re-evaluated. Randomized controlled clinical trials are largely missing.

Optical diagnosis of oral cavity lesions by label-free Raman spectroscopy.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers and frequently preceded by non-malignant lesions. Using Shifted-Excitation Raman Difference Spectroscopy (SERDS), principal component and linear discriminant analysis in native tissue specimens, 9500 raw Raman spectra of OSCC, 4300 of non-malignant lesions and 4200 of physiological mucosa were evaluated. Non-malignant lesions were distinguished from physiological mucosa with a classification accuracy of 95.3% (95.4% sensitivity, 95.2% specificity, area under the curve (AUC) 0.99). Discriminating OSCC from non-malignant lesions showed an accuracy of 88.4% (93.7% sensitivity, 76.7% specificity, AUC 0.93). OSCC was identified against physiological mucosa with an accuracy of 89.8% (93.7% sensitivity, 81.0% specificity, AUC 0.90). These findings underline the potential of SERDS for the diagnosis of oral cavity lesions.

Toward Tailoring the Degradation Rate of Magnesium-Based Biomaterials for Various Medical Applications: Assessing Corrosion, Cytocompatibility and Immunological Effects.

Magnesium (Mg)-based biomaterials hold considerable promise for applications in regenerative medicine. However, the degradation of Mg needs to be reduced to control toxicity caused by its rapid natural corrosion. In the process of developing new Mg alloys with various surface modifications, an efficient assessment of the relevant properties is essential. In the present study, a WE43 Mg alloy with a plasma electrolytic oxidation (PEO)-generated surface was investigated. Surface microstructure, hydrogen gas evolution in immersion tests and cytocompatibility were assessed. In addition, a novel in vitro immunological test using primary human lymphocytes was introduced. On PEO-treated WE43, a larger number of pores and microcracks, as well as increased roughness, were observed compared to untreated WE43. Hydrogen gas evolution after two weeks was reduced by 40.7% through PEO treatment, indicating a significantly reduced corrosion rate. In contrast to untreated WE43, PEO-treated WE43 exhibited excellent cytocompatibility. After incubation for three days, untreated WE43 killed over 90% of lymphocytes while more than 80% of the cells were still vital after incubation with the PEO-treated WE43. PEO-treated WE43 slightly stimulated the activation, proliferation and toxin (perforin and granzyme B) expression of CD8+ T cells. This study demonstrates that the combined assessment of corrosion, cytocompatibility and immunological effects on primary human lymphocytes provide a comprehensive and effective procedure for characterizing Mg variants with tailorable degradation and other features. PEO-treated WE43 is a promising candidate for further development as a degradable biomaterial.

A meta-analysis of the pros and cons of partial superficial parotidectomy versus superficial parotidectomy for the treatment of benign parotid neoplasms.

OBJECTIVES: Salivary gland tumors are predominantly benign and frequently localized in the parotid gland (P). The treatment consists primarily of surgical removal; however, the appropriate extent remains a subject of debate. In suitable tumors, superficial parotidectomy (SP) may be substituted for less invasive partial superficial parotidectomy (PSP) (I C). This systematic review analyzed the available literature, comparing PSP and SP with regards to several postoperative outcome parameters (O). MATERIALS AND METHODS: Established medical databanks were screened for articles evaluating outcomes of PSP compared with SP, published between 1955 and 2019. These data were assessed by pooled risk and odds ratios via meta-analysis. RESULTS: 11 studies with 1272 patients were included. There was no significant difference in tumor recurrence between PSP and SP (primary outcome). Furthermore, no differences in the occurrence of permanent facial nerve paralysis (FNP), salivary fistula, great auricular nerve analgesia, or hematoma were observed between the groups. However, PSP displayed significantly reduced rates of transient FNP, Frey's syndrome, scar deformity, and xerostomia, as well as shorter surgical time, compared with SP (secondary outcomes). CONCLUSION: Based on these data, PSP can be recommended as a surgical technique for the treatment of superficially located, small, benign parotid tumors.

TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone.

Osteoporosis is caused by increased bone resorption and decreased bone formation. Intermittent administration of a fragment of Parathyroid hormone (PTH) activates osteoblast-mediated bone formation and is used in patients with severe osteoporosis. However, the mechanisms by which PTH elicits its anabolic effect are not fully elucidated. Here we show that the absence of the homeodomain protein TG-interacting factor 1 (Tgif1) impairs osteoblast differentiation and activity, leading to a reduced bone formation. Deletion of Tgif1 in osteoblasts and osteocytes decreases bone resorption due to an increased secretion of Semaphorin 3E (Sema3E), an osteoclast-inhibiting factor. Tgif1 is a PTH target gene and PTH treatment failed to increase bone formation and bone mass in Tgif1-deficient mice. Thus, our study identifies Tgif1 as a novel regulator of bone remodeling and an essential component of the PTH anabolic action. These insights contribute to a better understanding of bone metabolism and the anabolic function of PTH.

Speech intelligibility in patients with oral cancer: An objective baseline evaluation of pretreatment function and impairment.

BACKGROUND: This study seeks to identify those factors that influence the pre-therapeutic speech intelligibility in patients with oral squamous cell carcinoma (OSCC). METHOD: A group of 172 patients (125 males, 47 females, mean age = 61 ± 11 a) with different OSCC stages ranging from T1 to T4 and N0 to N2 was examined for their speech intelligibility using a computerized measuring tool, and compared to a healthy reference group (30 males, 10 females, mean age = 59 ± 12 a). RESULTS: It was found that the pre-therapeutic speech intelligibility in patients with OSCC is decreased when compared to a healthy collective. Two demographic factors that influence speech intelligibility could be identified: sex and age. It was determined that the only disease-related factor that influences speech intelligibility before therapy is the location of the tumor. CONCLUSION: The results of this study reveal that a preoperative speech intelligibility impairment in patients suffering from OSCC occurs independent of tumor stage, size of the tumor and infiltration status.

Osteoid Osteoma of the Mandible - Clinical and Histological Findings.

BACKGROUND/AIM: Osteoid osteoma (OO) is a benign tumor characterized by the excessive formation of unmineralized bone matrix. It is mostly located in the long bones of the lower extremities or the spine, but can also occur in atypical locations. PATIENTS AND METHODS: Here we report on a rare case of OO in the mandible in an 18-year-old male patient with a simultaneous finding of a pilomatrixoma in the parietal region. Initially, a biopsy had been taken due to an unclear tumor mass and non-specific pain adjacent to tooth 46. RESULTS: The detailed radiographic and histopathological analysis revealed the diagnosis of OO in terms of a characteristic radiolucent nidus and structurally disorganized woven bone with osteoid, respectively. The tumor was subsequently completely resected resulting in a complete recovery of symptoms. CONCLUSION: As we demonstrate an infrequent finding of OO in the mandible, it is important to diagnose and treat this condition appropriately.