How to make full use of dental pulp stem cells: an optimized cell culture method based on explant technology.

Introduction: Dental pulp stem cells from humans possess self-renewal and versatile differentiation abilities. These cells, known as DPSC, are promising for tissue engineering due to their outstanding biological characteristics and ease of access without significant donor site trauma. Existing methods for isolating DPSC mainly include enzyme digestion and explant techniques. Compared with the enzymatic digestion technique, the outgrowth method is less prone to cell damage and loss during the operation, which is essential for DPSC with fewer tissue sources. Methods: In order to maximize the amount of stem cells harvested while reducing the cost of DPSC culture, the feasibility of the optimized explant technique was evaluated in this experiment. Cell morphology, minimum cell emergence time, the total amount of cells harvested, cell survival, and proliferative and differentiation capacity of DPSC obtained with different numbers of explant attachments (A1-A5) were evaluated. Results: There was a reduction in the survival rate of the cells in groups A2-A5, and the amount of harvested DPSC decreased in A3-A5 groups, but the DPSC harvested in groups A1-A4 had similar proliferative and differentiation abilities. However, starting from group A5, the survival rate, proliferation and differentiation ability of DPSC decreased significantly, and the adipogenic trend of the cells became more apparent, indicating that the cells had begun to enter the senescence state. Discussion: The results of our study demonstrated that the DPSC obtained by the optimized explant method up to 4 times had reliable biological properties and is available for tissue engineering.

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.

Dental Developmental Stages and Decayed, Missing, and Restored Teeth in Neurofibromatosis Type 1-affected Children and Adolescents.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited tumor predisposition disease with a highly variable phenotype. The influence of the characteristic NF1 tumors (neurofibromas) on dentition has not yet been examined in detail. The aim of the study was to assess the dentition of NF1 children and adolescents, considering the symmetry of tooth development. Material and Methods: The panoramic radiographs of 59 patients with a confirmed NF1 diagnosis were compared with 59 age-and-sex-matched controls. The stages of tooth development on the sides of the jaw, added to a score, were assessed. In addition, the number of filled or decayed teeth, and the number of retained or missing teeth were assessed. Results: The tooth development of both study groups is symmetrical for almost all parameters and in the same developmental stage according to the sum score of the tooth development stages. Discrete developmental delays of teeth, in particular in the oral area of facial plexiform neurofibroma (PNF) are noticeable. NF1 patients' teeth showed less decay and more restorations than that of the control group. The facial PNF (FPNF) does not impair emergence of deciduous teeth. Conclusions: Development of dentition of NF1 patients does not differ from the general population. However, FPNF with oral tumor components often prevent mesial movement of permanent molars and premolars, so these teeth do not develop contact (spacing), hardly emerge or may stay retained in bone. Oral PNF may have a low-retarding effect on some tooth root development (e.g., wisdom teeth). This effect is negligible when comparing the affected and unaffected sides of the jaw and is probably non-specific. Key words:Neurofibromatosis type 1, plexiform neurofibroma, dentition, mixed dentition, symmetry, oral health, tooth development.

Multiple central giant cell granuloma of the jaws: diagnostic signposts of Noonan syndrome and RASopathy.

Noonan syndrome (NS) is a phenotypically variable inherited multi-system disorder. Maxillofacial findings can be diagnostic, especially in the evaluation of discrete facial dysmorphia. Diagnostic landmark findings of therapeutic relevance for the jaws such as central giant cell granuloma (CGCG) are rare in NS. However, recent molecular genetic studies indicate that these rare, benign lesions are neoplasms and more common in specific syndromes grouped under the umbrella term RASopathies. A specialist surgical diagnosis can be helpful in identifying the underlying disease. This report outlines diagnosis and treatment of a case of CGCG for which jaw diagnosis became the key to identifying a syndromic disease.

Neurofibromatosis type 1-associated plexiform neurofibromas of the neck: topography of lesions and surgical treatment data of 69 patients.

PURPOSE: Plexiform neurofibromas (PNF) are rare tumors arising from peripheral nerve sheath cells. PNF are a hallmark in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. PNF often grow invasively and destructively, what may complicate surgical treatment. Data on frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data of NF1 patients. METHODS: Localization and treatment data of 69 NF1 patients with neck PNF were analyzed. Frequency of lesions was recorded in coded colors on schematic neck drawings. RESULTS: The tumors showed no side preference, were located in the entire area under investigation, and did not respect anatomical units/dermatomes. However, the sternocleidomastoid region was particularly frequently affected. The mean number of surgical measures per patient was 1.33. Complications were extensive swelling, hematoma, and bleeding. Histological assessment usually confirmed the clinical assessment of neoplasm. However, histologic differentiation of PNST reveals differences in between tumors that have been unified in clinical assessment as PNF. CONCLUSION: The color-coded, schematic overview of the frequency distribution of surgical neck interventions in NF1 patients with PNF proved a useful tool to gain assessment of preferred treatment needs. The imaging procedure may be suitable for controlling the external aspect of natural tumor development (growth, effects of aging) in the same way as the documentation of the post-surgical course. Treatment plans for patients with these tumors should consider that repeated interventions may be necessary to achieve a longer-term stable result.

The causal association between COVID-19 and herpes simplex virus: a Mendelian randomization study.

Introduction: The coronavirus disease 2019 (COVID-19) has emerged as a main global public health challenge. Additionally, herpes simplex virus type-1 (HSV-1) and type 2 (HSV-2) are widespread viruses that can cause orolabial herpes and genital herpes. Several clinical case reports have declared a possible association between the two, however, the causal relationship between them has not been clarified. Methods: This study utilized a Mendelian randomization (MR) approach for causality assessment between COVID-19 infection and HSV infection based on the latest public health data and Genome-Wide Association Study (GWAS) data. Multiple causal estimation methods, such as IVW, weighted median, simple mode, and weighted mode, were employed to validate the causal relation between COVID-19 infection and HSV infection, with COVID-19 infection, COVID-19 hospitalization, and severe COVID-19 as exposures, and HSV1/2 infection as the outcome. A reverse MR analysis was subsequently performed. Results: MR analysis exhibited that COVID-19 infection was relevant to a reduced risk of HSV1 infection (p=7.603239e-152, OR=0.5690, 95%CI=0.5455-0.5935, IVW). Regarding the effect of COVID-19 infection on HSV2, MR analysis suggested that COVID-19 infection was correlated with an augmented risk of HSV2 infection (p=6.46735e-11, OR=1.1137, 95%CI=1.0782-1.1502, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and COVID-19. Discussion: Altogether, COVID-19 infection might cause a decreased risk of HSV1 infection and an elevated risk of HSV2 infection.

Mandibular symmetry on posterior-anterior cephalograms of neurofibromatosis type 1 patients with facial plexiform neurofibroma.

Introduction: Neurofibromatosis type 1 (NF1) is an is an autosomal dominant heritable tumor predisposition syndrome.. Peripheral nerve sheath tumors (PNST) are a hallmark of NF1. Plexiform neurofibromas (PNF) are neoplasms that are characteristic of NF1, often causing disfiguring effects (e.g., on the face), and are considered precancerous lesions. Previous studies have shown that facial PNF (FPNF) have an impact on the shape of facial bones. This study examines deviations of mandibular symmetry from cephalometric reference planes considering the topography of FPNF. Material and methods: The posterior-anterior (PA) cephalograms of 168 patients with NF1 were examined. We compared three groups: patients with FPNF (n=74), with disseminated cutaneous neurofibroma (DNF (n=94)), and control subjects without NF1 (n=23). The PNF group was subtyped with respect to facial PNST type and location. Typical mandibular cephalometric reference points were determined (condyle, antegonion, and menton). Results: The skeletal measurement points of the mandible in FPNF patients often differ significantly from those of the DNF group. It has been proven that typical asymmetries of the median-sagittal measurement points are indicators of PNF. Differences within the trigeminal tumor spread patterns are indicated in the measured values. A local tumor effect (PNF) on the relation of the measurement points to the reference planes is made plausible by the study results. The investigations prove that tumor type (FPNF) and the number of FPNF affected branches of the trigeminal nerve may correlate with significant deviations of mandible from symmetry on PA projections. Conclusion: The presented study shows that characteristic patterns of mandibular deformity can be measured on standardized radiographs in NF1 patients with FPNF. Mandibular deformities imaged on standardized radiographs may be initial indicators of a previously unrecognized NF1. Tumor-associated alterations of the mandible should be considered in the classification systems of pathognomonic, diagnostically pioneering osseous findings in NF1. The radiological findings provide clues for planning mandibular osteotomies in NF1 patients, especially for assessing facial regions typically highly vascularized by tumor spread. Furthermore, the radiological findings are an indication of a tumor potentially invading and destroying adjacent masticatory and mimic muscle, findings that may have an influence on surgical measures (function, aesthetics, and wound healing).

Scoring system for assessing the symmetry of tooth development in mixed dentition.

Background: Human teeth develop sequentially and symmetrically in both halves of the jaws. Disorders of tooth development and eruption can be local or generalized. The symmetry comparison of tooth development is an essential measuring point to assess dentition. The aim of this study was the development of an easy-to-apply score that represents the tooth development of one side of the jaw to carry out side-specific development comparisons. Material and Methods: The stages of development and the state of health of the teeth were determined on orthopantomograms of 59 healthy children and adolescents applying acknowledged developmental standards of teeth. The individual stages of tooth development on one side of the jaw were combined into a numerical score. The sum score of each jaw side was compared. Results: The dental developmental score reveals the side differences of tooth development are small in children and adolescents with mixed dentition (n.s.). The change of teeth starts earlier in females. Conclusions: The presented score enables an easily applicable examination of the symmetry of tooth development in mixed dentition. Potential applications of the Score are to examine the influence of unilaterally manifest dento-skeletal developmental disorders on the change of teeth and the influence of deviating individual tooth development on neighboring teeth on one side. Key words:Dentition, development, symmetry, permanent teeth, deciduous teeth, oral health.Dentition, development, symmetry, permanent teeth, deciduous teeth, oral health.

Analysis of 5-Year-old children's oral health service utilization and influencing factors in Guizhou Province, China (2019-2020).

BACKGROUND: This study aimed to investigate the utilization patterns and factors related to oral health care for 5-year-old preschoolers based on Andersen's Behavioural Model in Guizhou Province, Western China. METHOD: A cross-sectional study of 4,862 5-year-old preschoolers in 66 kindergartens was conducted in 2019 and 2020. A basic oral examination and a survey of parents and grandparents were conducted to gather data on oral health services. The results were analysed using chi-square tests and logistic regression analysis. RESULT: The utilization rate of oral health services for children in Guizhou province was 20.5%. The dmft was 4.43, and the rate of caries was 72.2%. The average cost of a dental visit was higher in rural areas and higher for girls. Logistic regression analysis revealed that dmft ≥ 6 teeth, a history of toothache, starting toothbrushing at age ≤ 3 years and limited parental knowledge were the primary factors impacting dental visits. CONCLUSION: Needs factors such as severe oral conditions and pain in children are the main reasons for the utilization of these services. This study underscores the urgency to actively promote the importance of oral health and expand insurance coverage for oral health services.

Correlations between gut microbiota and lichen planus: a two-sample Mendelian randomization study.

Purpose: Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method. Methods: Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP. Results: According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP. Conclusion: The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.

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.

Neurofibromatosis Type 1-Associated Plexiform Neurofibromas of the Face and Adjacent Head Regions: Topography of Lesions and Surgical Treatment Data of 179 Patients.

Introduction: Facial plexiform neurofibromas (FPNF) are rare tumors frequently diagnosed in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. FPNF often grows invasively and destructively, which may complicate surgical treatment. Data on the frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data from a nationally networked reference center for the treatment of NF1 patients. Material and Methods: The localization and treatment data of 179 NF1 patients with FPNF were analyzed. Photographically documented tumors of the study area, further determined by imaging, were manually transferred to a facial scheme and digitized. The digitized registrations of the facial extensions of the tumors of each patient were overlaid in a single image (Photoshop™), so that the file of the facial scheme contained the sum of the tumor localization. Finally, the frequency of tumor localization was indicated with a color code. The frequency of tumor extension-related coded colors was applied to outline the lesions' topography on schematic face drawings (heat map). Results: The distribution of the tumors showed no side preference. The need for the treatment of patients with orbital/periorbital manifestations became evident in the graphic representations. Tumors do not respect anatomical units. However, the classification of the face according to dermatomes, especially the trigeminal nerve, offers indications of tumor spread and guides treatment planning. The mean number of surgical measures per patient was 2.21 (median: 1). Extensive swelling, hematoma, and delayed wound healing were all common postoperative complications. Conclusion: The color-coded, schematic overview of the frequency distribution of cutaneous tumor spread in NF1 patients with FPNF illustrates the importance of orbital/periorbital and cheek tumor manifestations in patients' treatment needs. The imaging procedure is suitable for controlling natural tumor growth in the same way as the documentation of the post-surgical course. Repeated interventions in the region are included in surgical planning of the progressing tumor disease.

Association between C-Reactive protein and periodontitis in an obese population from the NHANES 2009-2010.

BACKGROUND: Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: A cross-sectional analysis of data from 3602 participants in the 2009-2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). RESULTS: There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). CONCLUSION: Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.

Expression of Ras signaling pathway proteins and developmental factors in peripheral nerve sheath tumors of patients with neurofibromatosis type 1.

PURPOSE: To characterize expression of factors relevant for Ras signaling and developmental factors in a large series of peripheral nerve sheath tumors (PNST) obtained from patients with neurofibromatosis type 1 (NF1). MATERIALS AND METHODS: Tissue micro-array technique was applied to study 520 PNST of 385 NF1 patients by immunohistochemistry for mTor, Rho, phosphorylated MEK, Pax7, Sox9, and periaxin expression. PNST comprised cutaneous neurofibroma (CNF) (n = 114), diffuse neurofibroma (DNF) (n = 109), diffuse plexiform neurofibroma (DPNF) (n = 108), plexiform neurofibroma (PNF) (n = 110), and malignant PNST (MPNST) (n = 22). RESULTS: All proteins examined showed highest expression levels/highest frequency of expression in MPNST. Benign PNF with potential for malignant dedifferentiation expressed mTor, phosphorylated MEK, Sox9, and periaxin significantly higher/more frequently than other benign neurofibroma subtypes. CONCLUSION: In NF1-associated PNST, expression of proteins involved in Ras-signaling and development is upregulated not only in MPNST, but also in benign PNF with the potential for malignant dedifferentiation. The differences in protein expression may provide clues for understanding the therapeutic effects of substances applied for reduction of PNST in NF1.

Atypical neurofibromas reveal distinct epigenetic features with proximity to benign peripheral nerve sheath tumor entities.

BACKGROUND: Plexiform neurofibromas can transform into atypical neurofibromas (ANF) and then further progress to aggressive malignant peripheral nerve sheath tumors (MPNST). ANF have been described to harbor distinct histological features and frequent loss of CDKN2A/B. However, histological evaluation may be rater-dependent, and detailed knowledge about the molecular mechanisms of malignant transformation is scarce. In general, malignant transformation can be accompanied by significant epigenetic changes, and global DNA methylation profiling is able to differentiate relevant tumor subgroups. Therefore, epigenetic profiling might provide a valuable tool to distinguish and characterize ANF with differing extent of histopathological atypia from neurofibromas and MPNST. METHODS: We investigated 40 tumors histologically diagnosed as ANF and compared their global methylation profile to other peripheral nerve sheath tumors. RESULTS: Unsupervised class discovery and t-SNE analysis indicated that 36/40 ANF cluster with benign peripheral nerve sheath tumors with clear separation from MPNST. 21 ANF formed a molecularly distinct cluster in proximity to schwannomas. Tumors in this cluster had a frequent heterozygous or homozygous loss of CDKN2A/B and significantly more lymphocyte infiltration than MPNST, schwannomas, and NF. Few ANF clustered closely with neurofibromas, schwannomas, or MPNST, raising the question, whether diagnosis based on histological features alone might pose a risk to both over- and underestimate the aggressiveness of these lesions. CONCLUSIONS: Our data suggest that ANF with varying histological morphology show distinct epigenetic similarities and cluster in proximity to benign peripheral nerve sheath tumor entities. Future investigations should pay special respect to correlating this methylation pattern to clinical outcomes.

Characterization of Dental Pulp Stem Cell Populations in the Teeth of Patients With Neurofibromatosis Type 1 - Therapeutic Potential for Bone Tissue Engineering.

BACKGROUND/AIM: Neurofibromas (NF) are the most common benign nerve sheath tumors in the tongue, gingiva, major salivary glands, and jaw bones. Nowadays, tissue engineering is a revolutionary technique for reconstructing tissues. To explore the feasibility of using stem cells derived from NF teeth to treat orofacial bone defects, the differences in cell biological properties between an NF teeth group and Normal teeth group. PATIENTS AND METHODS: The intra-dental pulp tissues from each tooth were extracted. The cell survival rates, morphology, proliferation rates, cell activity, and differentiation abilities were contrastively analyzed between the NF teeth group and Normal teeth group. RESULTS: Between the two groups, there were no differences in the primary generation (P0) cells (p>0.05), the cell yield, and the time required for the cells to grow out of the pulp tissue and attach to the culture plate. Furthermore, no differences were found at the first generation (passage) between the two groups in colony formation rate and cell survival rate. The proliferation capacity, cell growth curve, and surface marker expression of dental pulp cells was not altered in the third generation (p>0.05). CONCLUSION: Dental pulp stem cells from NF teeth were successfully obtained and were not different from normal dental pulp stem cells. Although, clinical research using tissue-engineered bone to repair bone defects is still in its infancy, it will eventually enter the clinic and become a routine means of bone defect reconstruction treatment as related disciplines and technologies develop.

ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1.

Background: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder, predisposing development of benign and malignant tumours. Given the oncogenic potential, long-term surveillance is important in patients with NF1. Proposals for NF1 care and its specific manifestations have been developed, but lack integration within routine care. This guideline aims to assimilate available information on NF1 associated tumours (based on evidence and/or expert opinion) to assist healthcare professionals in undertaking tumour surveillance of NF1 individuals. Methods: By comprehensive literature review, performed March 18th 2020, guidelines were developed by a NF1 expert group and patient representatives, conversant with clinical care of the wide NF1 disease spectrum. We used a modified Delphi procedure to overcome issues of variability in recommendations for specific (national) health care settings, and to deal with recommendations based on indirect (scarce) evidence. Findings: We defined proposals for personalised and targeted tumour management in NF1, ensuring appropriate care for those in need, whilst reducing unnecessary intervention. We also incorporated the tumour-related psychosocial and quality of life impact of NF1. Interpretation: The guideline reflects the current care for NF1 in Europe. They are not meant to be prescriptive and may be adjusted to local available resources at the treating centre, both within and outside EU countries. Funding: This guideline has been supported by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS). ERN GENTURIS is funded by the European Union. DGE is supported by the Manchester NIHRBiomedical Research Centre (IS-BRC-1215-20007).

Unusual Findings in a Patient With Carney Complex due to a Novel PRKAR1A Mutation.

BACKGROUND/AIM: Carney complex (CNC) is a rare autosomal dominant tumor-predisposition syndrome with variable expression. Its main features are pigmentary skin lesions, soft-tissue myxomas, and endocrine overactivity or tumors. There is occasional overlap with other syndromes, and oligosymptomatic cases may escape diagnosis. This report describes the long journey of a patient until the diagnosis of CNC was finally made after a thorough diagnostic workup. CASE REPORT: The female patient was referred for treatment of a subcutaneous tumor of the lower abdomen. Medical reports detailed previous excisions of fibroma, neurofibroma and myxoma, and a malignant tumor of the cerebellopontine angle. The resected subcutaneous tumor was a myxoma. The identification of a previously unknown frameshift mutation in the gene for protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) in the patient confirmed the diagnosis of CNC. CONCLUSION: Patients with CNC may have highly variable clinical findings. Some rare lesions in CNC are more commonly recorded in other syndromes, making early diagnosis difficult in some cases. Genetic testing greatly facilitates diagnosis.

Corrigendum: DCBLD1 Overexpression is associated with a poor prognosis in head and neck squamous cell carcinoma.

[This corrects the article DOI: 10.3389/fimmu.2022.939344.].

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma.

Background: DCBLD1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the prognostic value and immune infiltration in head and neck squamous cell carcinoma remain unclear and need further research. Materials and Methods: DCBLD1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. The mRNA level in cell lines (SCC25 and CAL27) and gingival fibroblasts were detected using quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of DCBLD1 and clinical data in HNSCC. A nomogram was also established to predict the impact of DCBLD1 on prognosis based on Cox multivariate results. The methylation level of DCBLD1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of DCBLD1 were investigated using gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA). Results: The mRNA and protein expression levels of DCBLD1 were highly expressed in HNSCC tissue and cell lines. The Cox analyses demonstrate that highly expressed DCBLD1 is an independent prognosis marker (p < 0.05). ROC curve analysis showed the performance of DCBLD1 (area under the ROC curve: 0.948, sensitivity: 93.2%, specificity: 84.7%). The methylation was increased in HNSCC patients compared with normal subjects (p < 0.05) and was associated with poor prognosis at sites cg27642470 and cg21104965. Additionally, DCBLD1 expression is poorly associated with immune cell infiltration and immunological checkpoints PD-L1 and TIM-3. Conclusion: In head and neck squamous cell carcinoma, DCBLD1 is overexpressed, associated with poor patient prognosis. The detailed underlying mechanism merits further research.