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Background: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear. Methods: RNA sequencing (RNA‐seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT‐qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well. Results: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor–bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes. Conclusion: The results indicate a potential involvement of MMP13 in ameloblastoma‐related bone resorption and progression. [ABSTRACT FROM AUTHOR]

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Whole‐exome sequencing (WES) analysis of an expansive case florid cemento‐osseus dysplasia were reported for the first time. Also, the new potential candidate genes were reported to expand our knowledge about their molecular pathogenesis. We report a case of expansive florid cemento‐osseus dysplasia in a 32‐year‐old female patient who presented an expansive tumoral lesion in the anterior mandible. As florid cemento‐osseus dysplasia have only been molecularly investigated using targeted‐sequencing, fragments of the lesion were collected and subjected to molecular investigation using WES to assess somatic mutations as well as copy number alterations. No gains and losses of chromosomal arms or segments longer than 1 Mb were detected. Our findings revealed a pathogenic stopgain variant at the KIF5C gene, a stoploss variant at MAPK10, and missense SNV at COL6A2 at DCDC1, suggesting potential candidate genes associated with florid cemento‐osseus dysplasia. [ABSTRACT FROM AUTHOR]

The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal was to reveal individual variability and lateralization of FAT and its structure–function correlations in language processing. The study utilized diffusion MRI data from 1065 subjects obtained from the Human Connectome Project. Automated tractography using DSI Studio software was employed to map white matter bundles, and the results were examined to study the population variation of the FAT. Additionally, anatomical dissections were performed to validate the fiber tracking results. The tract‐to‐region connectome, based on Human Connectome Project‐MMP parcellations, was utilized to provide population probability of the tract‐to‐region connections. Our results showed that the left anterior FAT exhibited the most substantial individual differences, particularly in the superior and middle frontal gyrus, with greater variability in the superior than the inferior region. Furthermore, we found left lateralization in FAT, with a greater difference in coverage in the inferior and posterior portions. Additionally, our analysis revealed a significant positive correlation between the left FAT inferior coverage area and the performance on the oral reading recognition (p =.016) and picture vocabulary (p =.0026) tests. In comparison, fractional anisotropy of the right FAT exhibited marginal significance in its correlation (p =.056) with Picture Vocabulary Test. Our findings, combined with the connectivity patterns of the FAT, allowed us to segment its structure into anterior and posterior segments. We found significant variability in FAT coverage among individuals, with left lateralization observed in both macroscopic shape measures and microscopic diffusion metrics. Our findings also suggested a potential link between the size of the left FAT's inferior coverage area and language function tests. These results enhance our understanding of the FAT's role in brain connectivity and its potential implications for language and executive functions. [ABSTRACT FROM AUTHOR]

Dominance of neotropical tree communities by a few species is widely documented, but dominant trees show a variety of distributional patterns still poorly understood. Here, we used 503 forest inventory plots (93,719 individuals ≥2.5 cm diameter, 2609 species) to explore the relationships between local abundance, regional frequency and spatial aggregation of dominant species in four main habitat types in western Amazonia. Although the abundance‐occupancy relationship is positive for the full dataset, we found that among dominant Amazonian tree species, there is a strong negative relationship between local abundance and regional frequency and/or spatial aggregation across habitat types. Our findings suggest an ecological trade‐off whereby dominant species can be locally abundant (local dominants) or regionally widespread (widespread dominants), but rarely both (oligarchs). Given the importance of dominant species as drivers of diversity and ecosystem functioning, unravelling different dominance patterns is a research priority to direct conservation efforts in Amazonian forests. [ABSTRACT FROM AUTHOR]

Background: This study presents a case series and scoping review of oral melanoacanthoma to examine its clinical, histopathological, and immunohistochemical characteristics. Methods: Nine cases of oral melanoacanthoma were included in the case series. Clinical data were collected from biopsy charts. Hematoxylin–eosin and immunohistochemistry for TRP2, CD3, and CD20 were done. For the scoping review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Results: Case series: The mean age was 46.8 years (female‐to‐male ratio 2:1). Lesion's mean size was 11.0 mm (±9.3). Lesions were mainly macular (77.8%) with brown or black coloration (88.9%) and often affected multiple sites (44.4%). The evolution time ranged from 15 days to 96 months. Lesions commonly showed epithelial acanthosis (66.7%), spongiosis (55.6%), exocytosis (77.8%), melanin incontinence (88.9%), and inflammatory infiltrate in the lamina propria (77.8%), from which all showed lymphocytes. TRP2‐positive melanocytes were identified in the basal and spinous layer of all cases, and in the superficial layer of three cases. CD3‐positive cells predominate over the CD20‐positive. Scoping review: 85 cases of oral melanoacanthoma were retrieved from 55 studies. Patients were primarily female (female‐to‐male ratio 2.2:1), black‐skinned (64.1%), with a mean age of 36.13 (± 17.24). Lesions were flat (81.9%), often brown (62.4%). Buccal mucosa was the preferred site (32.9%), followed by multiple sites (28.2%). Conclusion: Oral melanoacanthoma mainly affects women across a wide age range, with lesions commonly appearing as brown/black macules, particularly on the buccal mucosa. TRP2‐positive melanocytes and T‐lymphocytes were consistently found and could participate in oral melanoacanthoma pathogenesis. [ABSTRACT FROM AUTHOR]

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism‐associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell‐rich lesions, including non‐ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell‐rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell‐rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer‐associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism‐associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell‐rich mimics (NOF, ABC, GCTB, and chondroblastoma). [ABSTRACT FROM AUTHOR]

This article discusses the molecular drivers and pathogenesis of giant cell granulomas of the jaws (CGCGJ) and their implications for targeted therapy. The study found that CGCGJ shares histopathological similarities with other giant cell-rich lesions, but does not exhibit certain mutations found in those lesions. Recent advancements in molecular studies have identified somatic mutations in genes such as KRAS, TRPV4, and FGFR1 in CGCGJ. The article also explores the association between CGCGJ and certain syndromes, as well as the potential use of TRPV4 inhibitors as a therapeutic approach for more aggressive cases. [Extracted from the article]

This article discusses a case of plaque-like cutaneous mucinosis (PCM) in a patient with KRAS-mutated giant cell granuloma of the jaw. PCM is a condition characterized by lichenoid papules, nodules, or plaques with glycosaminoglycan deposition in the dermis. The patient in this case had PCM overlying a benign bone-resorbing neoplasia of the jaw called central giant cell granuloma (CGCG). The PCM rapidly resolved following surgical resection of the tumor. The article also mentions other paraneoplastic dermatoses associated with oral neoplasia and provides information on the diagnosis and differential diagnosis of PCM. [Extracted from the article]

Strategic planning has been increasingly used by local governments worldwide to boost performance. While this can be seen as a technical and political process, the relationship between managerial qualifications, political context and achievement of strategic goals in local governments has been scarcely studied. This study explores these relationships using data from 137 Colombian municipalities at the middle and end of the 2016–2019 mayoral term. Findings suggest that midterm strategic goal achievement is associated with mayoral experience, particularly in the national government where the tradition of strategic planning is better established, and this relationship increases with higher levels of municipal council support. Certain traits of the chief planning officer, appointed by the mayor, also correlate positively with midterm goal achievement. End‐term goal achievement is mainly associated with midterm paths. This research contributes to the performance management literature by highlighting the political‐managerial interplay in strategic goal achievement. [ABSTRACT FROM AUTHOR]

Background: Unicystic ameloblastoma is an encapsulated odontogenic neoplasm with a single cyst cavity. The conservative or aggressive surgical approaches used to treat the tumor directly affect recurrence rates. However, there is a lack of a standard protocol that can guide its management. Study Design: We retrospectively reviewed the clinicopathological findings and therapeutical procedures of 12 unicystic ameloblastoma cases treated by the same surgeon during the past 20 years. Methods: All cases of unicystic ameloblastoma diagnosed by biopsy and treated by the same surgeon between 2002 and 2022 were reviewed. Eligibility criteria were patients with completely filled‐out charts containing the follow‐up period and confirmation of the diagnoses based on the microscopic findings of the whole excised specimens. Data collected were categorized into clinical, radiographic, histological, surgical, and recurrence aspects. Results: There was a female predilection (2:1), and ages ranged between 18 and 61 years (mean: 27.25, ±12.45). Almost all (92%) affected the posterior mandible. Radiographically, the mean length of the lesions was 46.14 mm ± 14.28 mm which 92% were unilocular and 8.3% multilocular. Root resorption (n = 7, 58%), tooth displacement (n = 9, 75%), and cortical perforation (n = 5, 42%) were also observed. The mural histological subtype corresponded to 9 (75%) of the cases. The same conservative protocol was performed in all cases. The follow‐up period ranged between 12 and 240 months (~62 ± 65) and recurrence occurred in only one patient (8%). Conclusion: Our findings suggest a conservative approach should be the first option for unicystic ameloblastoma treatment, even for those with mural proliferation. [ABSTRACT FROM AUTHOR]

Soft tissue tumours (STT) are a heterogeneous group of benign, malignant, and intermediate/borderline mesenchymal tumours. In the oral and maxillofacial region, less than 3% of all lesions correspond to benign STT and <1% are sarcomas. Overlapping microscopic features may lead to quite challenging diagnostic processes. Translocations and fusion genes are frequent, and type‐specific genetic alterations are detected in these tumours. The detection of such alterations by classic cytogenetic, FISH, RT‐PCR or NGS can help to define the diagnosis. This narrative review aims to review fusion genes reported for STT that affect the oral cavity and their use in diagnostic molecular pathology. Basic concepts regarding mechanisms of fusion genes formation are presented to clarify this information for surgical pathologists. The chromosomal rearrangements and fusion genes of adipocytic, fibroblastic and myofibroblastic, vascular, pericytic, smooth muscle, skeletal muscle, chondro‐osseous, and uncertain origin STT are summarised. The advance in molecular pathology techniques has led not only to a better understanding of the molecular pathogenesis of STT, but also to the development of helpful diagnostic tools. Therefore, it is important for the oral and head and neck pathologists to familiarise with the signature rearrangements and fusion genes for each tumour. [ABSTRACT FROM AUTHOR]

Clinical Key Message: We present a case of recurring ameloblastoma in soft tissue, for which we have estimated the growth rate of the lesion. This information could help clinicians to establish follow‐up protocols for the early diagnosis of recurrent ameloblastomas. In the present paper, we present a case of recurring ameloblastoma in soft tissue, for which we have estimated the growth rate of the lesion. The area of the whole resected specimen was measured using the ImageJ guide for complex object area. After dividing the area of the recurrent tumor by the number of years during the follow‐up, we found that the lesion growth rate was 5.3 cm2 per year. Although further studies are still necessary in the literature to assess the growth rate of ameloblastoma, the present report shows a different methodology to estimate it. This information could help clinicians to establish follow‐up protocols for the early diagnosis of recurrent ameloblastomas. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis is a chronic inflammation of the nasal mucosa and nasal polyps are present in ~25%–30% of cases (chronic rhinosinusitis with nasal polyps [CRSwNP]). CRSwNP is associated with significant morbidity and decreased quality of life, making it clinically important. Inflammation leads to DNA damage and DNA mutations occur in some inflammatory diseases. Notably, mutations in KRAS, BRAF, and EGFR have been reported in different human benign and malignant neoplastic lesions. In addition, KRAS mutations have also been reported in non‐neoplastic tissues under chronic inflammatory conditions. Importantly, KRAS mutations have been reported in oncocytic sinonasal papillomas and sinonasal squamous cell carcinoma associated with oncocytic sinonasal papilloma and EGFR mutations have been reported in sinonasal adenocarcinoma, inverted sinonasal papilloma, and sinonasal squamous cell carcinoma associated with inverted sinonasal papilloma. The molecular pathogenesis of nasal polyps remains unclear. Therefore, the present study aimed to investigate the presence of KRAS, BRAF, and EGFR pathogenic mutations in CRSwNP. Methods: Fourteen chronic rhinosinusitis‐associated nasal polyp samples were direct sequenced, targeting KRAS exons 2, 3, and 4 (encompassing important hotspot mutations, including codons 12, 13, 61 and 146), BRAF exons 11 and 15, and EGFR exons 19 and 20. Results: No pathogenic mutations were detected in the sequenced regions of KRAS, BRAF, and EGFR genes. Conclusion: This finding suggests that mutations in these genes are not a frequent event in CRSwNP, and, if they occur, they might represent marginal events at best. [ABSTRACT FROM AUTHOR]

Throughout the centuries, the world's outstanding scientists and research groups have gathered their efforts to characterise the initiation and progression of malignant neoplasms. The temporal dissection of tumourigenesis provided by phylogenetic studies is one of the milestones in understanding cancer; however, some black boxes are still unsolved. Currently, there is no consensus regarding the development of oral squamous cell carcinoma (OSCC), the leading cancer of the head and neck region. Oral epithelial dysplasia (OED) may precede oral cancer and, occasionally, be clinically evident as white, red or mixed mucosal lesions, called oral potentially malignant disorders (OPMD). In a stepwise view of oral carcinogenesis, OED and OPMD have been considered harbingers of oral cancer. Nevertheless, the malignant transformation of OPMD is a rare event. Most of these disorders remain benign and can even regress, making it challenging to formulate evolutionary hypotheses for OSCC initiation. Deciphering OED evolution is vital to highlight the potential drivers of oral carcinogenesis and molecular targets for OSCC preventative and therapeutic strategies. This narrative review synthesises the main concepts of evolutionary theories and discusses which of them better explains OED development and malignant transformation. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)‐based histology image analyses could accelerate the discovery of better OC progression risk models. Methods: Our CNN‐based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could identify abnormal morphological features of the oral epithelium. By applying this model to OL slides, we hypothesized that the extent of OC‐like features identified in the OL epithelium would correlate with its progression risk. The OMRS model scored and categorized the OL cohort (n = 62) into high‐ and low‐risk groups. Results: OL patients classified as high‐risk (n = 31) were 3.98 (95% CI 1.36–11.7) times more likely to develop OC than low‐risk ones (n = 31). Time‐to‐progression significantly differed between high‐ and low‐risk groups (p = 0.003). The 5‐year OC development probability was 21.3% for low‐risk and 52.5% for high‐risk patients. The predictive power of the OMRS model was sustained even after adjustment for age, OL site, and OL dysplasia grading (HR = 4.52, 1.5–13.7). Conclusion: The ORMS model successfully identified OL patients with a high risk of OC development and can potentially benefit OC early diagnosis and prevention policies. [ABSTRACT FROM AUTHOR]

When an executive departs, some organizations experience a vacancy while others do not. Recent research shows that the occurrence and length of vacancy instances within and across sectors varies widely. However, the causes of such variance in vacancies have yet to be carefully addressed by public management research. This study explores the determinants of executive vacancy, focusing specifically on organizational‐level characteristics of size, performance, and sector as well as the role of anticipation of a departure. We use data from public and private US doctoral universities to identify 230 leadership transitions between 1993 and 2013. In this context, we find that anticipation of departure is an extremely strong predictor of vacancy. Moreover, private universities are significantly less likely than their public counterparts to experience executive vacancy while organizational performance and size do not appear to influence vacancy. [ABSTRACT FROM AUTHOR]

Background: TERT promoter mutations increase telomerase activity, conferring cell immortality. The coexistence of TERT promoter mutations with BRAFV600E is associated with aggressiveness. Ameloblastoma and ameloblastic carcinoma are infiltrative neoplasms that harbor BRAFV600E; however, it remains unknown if these odontogenic tumors also show TERT promoter mutations. Methods: Genomic DNA of paraffin‐embedded ameloblastomas (n = 6) and ameloblastic carcinomas (n = 3) were Sanger‐sequenced to assess the hotspot TERT promoter mutations C228T and C250T. BRAFV600E status was screened by TaqMan allele‐specific quantitative polymerase chain reaction. Results: None of the samples harbored TERT promoter mutations. The BRAFV600E mutation was positive in 3 of 6 of ameloblastomas and in 1 of 3 of ameloblastic carcinomas. Conclusion: The absence of TERT promoter mutation in the samples indicates that this molecular event is not relevant to the tumors' pathogenesis. Further studies are necessary to explore undefined genetic or epigenetic mechanisms related to TERT‐upregulation in ameloblastoma, and the telomerase activity in ameloblastic carcinoma. [ABSTRACT FROM AUTHOR]

The article emphasizes the need for increased focus on the salivary glands in the context of Sjögren's syndrome, particularly in relation to COVID-19. Topics discussed include the impact of COVID-19 on salivary gland function in patients with Sjögren's syndrome, the potential exacerbation of symptoms due to the virus, and the implications for patient management and treatment strategies.

Objective: We aimed to assess which metabolic pathways would be implicated in the phenotypic changes of the epithelial lining of odontogenic keratocyst after marsupialization, comparing pre‐ and post‐marsupialized lesions with adjacent oral mucosa. Materials and Methods: Eighteen formalin‐fixed and paraffin‐embedded tissues from six subjects were divided into three paired groups: odontogenic keratocyst pre‐ (n = 6) and post‐marsupialization (n = 6), and adjacent oral mucosa (n = 6). The metabolic pathways found in these groups were obtained by high‐performance liquid chromatography‐mass spectrometry‐based untargeted metabolomics performed. Results: Through putative metabolite annotation followed by pathway enrichment and predictive analysis with automated algorithms (Mummichog and Gene Set Enrichment Analysis), we found differences in many cellular processes that may be involved in inflammation, oxidative stress response, keratinocyte‐basal membrane attachment, differentiation, and proliferation functions, all relevant to odontogenic keratocyst pathobiology and the phenotype acquired after marsupialization. Conclusion: Our study was able to identify several metabolic pathways potentially involved in the metaplastic changes induced by marsupialization of odontogenic keratocysts. An improved comprehension of this process could pave the way for the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews (SRs) have become a popular approach for evidence‐based practice, being considered a lens through which evidence is viewed and applied. However, several published studies have been identified as scoping reviews rather than SRs. This methodological error can negatively impact clinical decision‐making or new research conceptualization. Aim: This letter focuses on the increasing number of SRs in oral pathology and medicine, highlighting the most frequent methodological mistakes. Results: We providing general guidance to help researchers conceptualize better their SRs and for the critical evaluation of SRs by scientific journal reviewers. Conclusion: Clinicians, pathologists, and reviewers, must ensure the quality of the published information. [ABSTRACT FROM AUTHOR]

Objectives: Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas. Materials and Methods: The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin‐embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at −196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real‐time PCR (qPCR) assay. The ameloblastoma paraffin‐embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage. Results: There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry. Conclusion: Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial fission and fusion processes are known as mitochondrial dynamics and the occurrence of imbalances in the mitochondrial activity is related to the pathogenesis of many human cancers. However, the importance of mitochondrial dynamics in malignant salivary gland tumours remains unknown. Therefore, we aimed to investigate its prognostic significance in adenoid cystic carcinoma. Methods: Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2 and OPA1 proteins. Clinical data were retrieved from the patients' medical files, including specific and disease-free survival data. Results: It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, and 49.1%, 21.1%, 22.8% and 24.6% strongly positive for FIS1, MFN1, MFN2 and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumour. The higher expression of MFN2 was associated with solid microscopic pattern (p = 0.016). DRP1 overexpression showed a trend towards a shorter overall survival (p = 0.054), while negative/weak OPA1 showed a trend towards a lower disease-free survival (p = 0.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. Conclusion: In conclusion, mitochondrial dynamics markers do not seem to carry a prognostic significance for adenoid cyst [ABSTRACT FROM AUTHOR]

Background: Giant cell granuloma of the jaws are benign osteolytic lesions of the jaws. These lesions are genetically characterized by mutually exclusive somatic mutations at TRPV4, KRAS, and FGFR1, and a fourth molecular subgroup which is wild-type for the three mutations. Irrespective of the molecular background, giant cell granulomas show MAPK/ERK activation. However, it remains unclear if these mutations lead to differences in their molecular signaling in giant cell granulomas.Methods: Metabolomics, proteomics, and phosphoproteomics analyses were carried out in formalin-fixed paraffin-embedded samples of giant cell granuloma of the jaws. The study cohort consisted of five lesions harboring mutations in FGFR1, six in KRAS, five in TRPV4, and five that were wild-type for these mutations.Results: Lesions harboring KRAS or FGFR1 mutations showed overall similar proteomics and metabolomics profiles. In all four groups, metabolic pathways showed similarity in apoptosis, cell signaling, gene expression, cell differentiation, and erythrocyte activity. Lesions harboring TRPV4 mutations showed a greater number of enriched pathways related to tissue architecture. On the other hand, the wild-type group presented increased number of enriched pathways related to protein metabolism compared to the other groups.Conclusion: Despite some minor differences, our results revealed an overall similar molecular profile among the groups with different mutational profile at the metabolic, proteic, and phosphopeptidic levels. [ABSTRACT FROM AUTHOR]

Purpose: To investigate and compare the demographic data, occurrence of recurrence and metastasis, and survival prognosis between ameloblastic carcinoma (AC) and metastasizing ameloblastoma (MA), based on appropriate and currently accepted eligible diagnostic criteria, in a systematic review of the literature.Methods: An electronic search was undertaken, last updated in December 2021. Eligibility criteria included publications having enough clinicopathological information to confirm the diagnosis of these tumors.Results: Seventy-seven publications reporting 85 ACs and 43 MAs were included. Both tumors were more frequent in mandible and showed different clinical profiles regarding patients' sex and age. There was no difference in the estimated cumulative survival between patients diagnosed with these tumors. Metastases mainly affected the lungs, followed by cervical lymph nodes. The mean time between the first metastasis and the last follow-up was higher for MA (p = 0.021). In addition, MA patients remained alive longer than AC patients after the first metastasis diagnosis (p = 0.041). Considering only the cases that metastasized, a higher ratio of AC patients died in comparison to MA patients (p = 0.003). The occurrence of recurrence was associated with a conservative primary treatment with both AC (p < 0.001) and MA tumors (p = 0.017). Multiple recurrent events were associated with conservative primary therapies with MA (p < 0.001) but not with AC (p = 0.121).Conclusion: In addition to some demographic differences, ACs that metastasize present a worse prognosis than MA. As conservative procedures are associated with multiple recurrent events, this treatment modality should be avoided for both tumors. [ABSTRACT FROM AUTHOR]

Background: Fibrous dysplasia (FD) and cemento‐ossifying fibroma (COF) are the most common gnathic fibro‐osseous lesions. These diseases exhibit remarkable overlap of several clinicopathological aspects, and differential diagnosis depends on the combination of histopathological, radiographic, and clinical aspects. Their molecular landscape remains poorly characterized, and herein, we assessed their proteomic and phosphoproteomic profiles. Methods: The quantitative differences in protein profile of FD and COF were assessed by proteomic and phosphoproteomic analyses of formalin‐fixed paraffin‐embedded tissue samples. Pathway enrichment analyses with differentially regulated proteins were performed. Results: FD and COF exhibited differential regulation of pathways related to extracellular matrix organization, cell adhesion, and platelet and erythrocytes activities. Additionally, these lesions demonstrated distinct abundance of proteins involved in osteoblastic differentiation and tumorigenesis and differential abundance of phosphorylation of Ser61 of Yes‐associated protein 1 (YAP1). Conclusions: In summary, despite the morphological similarity between these diseases, our results demonstrated that COF and DF present numerous quantitative differences in their proteomic profiles. These findings suggest that these fibro‐osseous lesions trigger distinct molecular mechanisms during their pathogenesis. Moreover, some proteins identified in our analysis could serve as potential biomarkers for differential diagnosis of these diseases after further validation. [ABSTRACT FROM AUTHOR]

Previously, by employing 3D organotypic tissue culture and patient‐derived xenograft (PDX) model, oral myxoma response to a MAPK/MEK inhibitor was observed. Gross examination of the tumour fragments obtained after 55 days of PDX grafting revealed increased capsule vascularization. Microscopic analyses showed blood capillaries intermixed with myxoma cells, but the origin of these capillaries, from mice or humans, was not established. This study aimed to investigate whether the endothelial cells observed in the myxoma PDX model are derived from the mouse or from the primary human tumour. Immunohistochemistry was performed on five tumour fragments from the PDX of myxoma after 55 days of implantation in mice. Immunopositivity for antibodies against human (HLA‐ABC) and mouse (H2 Db/H2‐D1) major histocompatibility complex class I (MHCI) was assessed in the endothelial cells. The endothelial cells in the PDX fragments revealed a membrane staining for the human MHCI protein in the PDX tumour and adjacent connective tissue capsule, indicating that capillaries were derived from the human tumour fragment. Considering the probable human origin of the endothelial cells from capillary blood vessels in the myxoma PDX, we conclude that this PDX model is an interesting model to study myxoma angiogenesis. [ABSTRACT FROM AUTHOR]

Dental follicles are involved in odontogenesis, periodontogenesis, and tooth eruption. Dental follicles are unique structures, considering that their remnants can persist within the jawbones after odontogenesis throughout life if the tooth does not erupt. Pathological changes may occur in these tissues as individuals age. The changes range from benign to life threatening. Thus, the assessment of age‐related changes in dental follicles associated with unerupted teeth is of paramount importance. In this review, we summarize the physiological roles and changes in dental follicles in odontogenesis, tooth eruption, and aging, in addition to the pathological changes associated with these structures. We encourage investigators to consider this peculiar tissue as a unique model and explore its potential to clarify its importance from the viewpoints of developmental biology, tissue physiology, and pathology. Key Findings: Dental follicle has important roles in odontogenesis, periodontogenesis, and tooth eruption. When tooth eruption is impaired, remnants of dental follicle can permanently persist in the jaws.Oral pathologists tend to refer to the tissue associated with unerupted teeth as "dental follicles". This term should be interpreted with caution, considering that these are remnants of the dental follicle.As individuals age, dental follicles associated with unerupted teeth undergo morphological and molecular changes. Notably, odontogenic cysts and tumors can originate from dental follicles associated with unerupted teeth.Herein, we integrated information on dental follicles from development to aging, and pathological changes. [ABSTRACT FROM AUTHOR]

Background: Central giant cell granulomas (CGCG) of the jaws are osteolytic lesions that may behave aggressively and respond poorly to surgery. Microscopically, in addition to giant cells, there is a mononuclear cell population composed of macrophage/monocytic cells and spindle‐shaped cells of mesenchymal origin. Seventy two percent of these tumours harbour mutually exclusive TRPV4, KRAS and FGFR1 mutations. We aimed to assess the mutational status of mononuclear and giant cells and the osteogenic potential of stromal cells in vitro and in vivo. Methods and Results: We screened CGCG for signature mutations and used laser‐capture microdissection to demonstrate that the mutations are restricted to the mononuclear cells. Additionally, we established CGCG primary cell culture and observed that the cells retained the mutations throughout passages. By flow cytometry, we observed predominance of CD14−CD51−CD61− cells, consistent with the expected profile for stromal cells. Considering the mesenchymal origin of stromal cells, we assessed the osteogenic differentiation potential of CGCG cells in culture by cytochemistry (von Kossa and alizarin red staining), alkaline phosphatase (ALP) activity assay and gene expression of osteogenic markers. CGCG cells presented self‐capacity to increase ALP levels in a time‐dependent manner and under osteogenic induction presented increasing number of calcium deposits, and overall higher expression of osteocalcin, RUNX2, ALPL and osteopontin than cells without osteogenic induction. A patient‐derived xenograft model for CGCG was established, and osteoid material deposition was observed. Conclusion: Collectively, the results confirm that the signature mutations are restricted to stromal cells in CGCG, and the in vitro and in vivo results support that these cells have the capacity to differentiate into osteoblasts, in line with the bone formation often observed in the stroma of these lesions. [ABSTRACT FROM AUTHOR]

Zooplankton plays a pivotal role in sustaining the majority of marine ecosystems. The distribution patterns and diversity of zooplankton provide key information for understanding the functioning of these ecosystems. Nevertheless, due to the numerous cryptic and sibling species and the lack of diagnostic characteristics for early developmental stages, the identification of the global‐to‐local patterns of zooplankton biodiversity and biogeography remains challenging in different research fields. The spatial and temporal changes in the zooplankton community in the open waters of the southern Gulf of Mexico were assessed using metabarcoding analysis of the V9 region of 18S rRNA and mitochondrial cytochrome oxidase c subunit I (COI). Additionally, a multiscale analysis was implemented to evaluate which environmental predictors may explain the variability in the structure of the zooplankton community. Our findings suggest that the synergistic effects of dissolved oxygen concentration, temperature, and longitude (intended as a proxy for still unidentified predictors) may explain both spatial and temporal zooplankton variability even with low contribution. Furthermore, the zooplankton distribution probably reflects the coexistence of three heterogeneous ecoregions and a bio‐physical partitioning of the studied area. Finally, some taxa were either exclusive or predominant with either 18S or COI markers. This may suggest that comprehensive assessments of the zooplankton community may be more accurately met by the use of multilocus approaches. [ABSTRACT FROM AUTHOR]

Background: Hybrid odontogenic lesions combine histopathological characteristics of two or more odontogenic cysts and/or tumours. The aim of this study was to evaluate the available data on hybrid odontogenic lesions (HOL) and to analyse their epidemiological/clinical features and biological behaviour. Methods: An electronic search was done in January 2021 using multiple databases. Eligibility criteria encompassed publications with sufficient clinical and histological information to confirm the tumours' diagnoses. Results: A total of 147 articles were included in this study, comprising 203 cases. Calcifying odontogenic cyst associated with odontoma (COC/OD) (37/18.2%) was the most common HOL. Females were more affected with a mean age of 24.9 years. Lesions presented as asymptomatic swellings, with a mean evolution time of 8.2 months (0.3–96), and mean tumour size of 4.8 cm (0.3–7). Radiographic aspects frequently showed radiolucent (139/68.4%) and unilocular (52/25.6%) images with well‐defined limits (48/23.6%). The lesions mostly affected mandibular pre‐molars (69/34%) and mandibular molars (69/34%) regions. Enucleation (89/43.8%) and surgical excision (59/29%) were the most common treatment modalities. The mean follow‐up time was 33.8 months (0.5–216 months) and recurrences were observed in four cases (1.9%), all of which were central odontogenic fibroma associated with central giant cell granuloma (COF/CGCG). Conclusion: COC/OD is the most common HOL and recurrence is a rare event, being usually associated with the diagnosis of COF/CGCG. [ABSTRACT FROM AUTHOR]

Salivary gland tumours present a pleomorphic and complex morphology and, apart from the most common neoplasms with well‐established histopathological criteria, may create diagnostic difficulty for histopathologists. The majority of salivary gland tumours occur in the parotid gland and the use of ultrasound guided parotid biopsy (US‐PB) has increased. US‐PB in contrast with fine needle aspiration (FNA), which is an easy and relatively painless technique, is performed under local anaesthesia, usually by radiologists. US‐PB offers some advantages over the FNA such as tumour grading and the possibility of performing immunohistochemistry. We report our experience of the diagnostic value of US‐PB in a large, referral centre in the United Kingdom. [ABSTRACT FROM AUTHOR]

Although Washington state sanctuary policies of 2017 prohibit collaboration between local law enforcement and federal immigration enforcement in noncriminal cases, compliance with sanctuary policies has not been systematically studied. We explore information practices and collaboration between local law enforcement and federal immigration enforcement in Grant County, Washington, based on records from November 2017 to May 2019 obtained by the University of Washington Center for Human Rights through Public Records Act (PRA) requests. Qualitative analysis of over 8,000 pages reveals a baseline of passive and active information sharing and collaboration between local law enforcement and federal immigration agencies before Washington sanctuary laws went into effect in May 2019, a practice that needs to stop if agencies are to comply with the laws. We employ a systematic methodology to obtain (through PRA and other Access to Information requests) and analyze official records through qualitative content analysis, to monitor and hold local law enforcement accountable in their compliance with sanctuary laws. This method can be used to examine law enforcement information behaviors in other counties in Washington, and in other states that offer sanctuary protections, as a way to monitor compliance with sanctuary laws and strengthen the protection of immigrants' rights. [ABSTRACT FROM AUTHOR]

Background: Adenoid ameloblastoma is a rare epithelial neoplasm, histologically characterized by the presence of ameloblastoma‐like features, duct‐like structures, epithelial whorls, and cribriform architecture. Dentinoid material is usually present. Some advocate adenoid ameloblastoma is an ameloblastoma variant. However, there are overlapping features not only with ameloblastoma, but also with adenomatoid odontogenic tumor. Most ameloblastomas are characterized by the presence of BRAF p.V600E mutations and adenomatoid odontogenic tumors harbor signature KRAS mutations. The molecular features of adenoid ameloblastoma remain unknown. Methods: Nine adenoid ameloblastoma cases were screened by TaqMan allele‐specific qPCR to assess BRAF p.V600E, ameloblastoma signature mutation, and KRAS p.G12V and p.G12R, adenomatoid odontogenic tumor signature mutations. Results: BRAF and KRAS mutations were not detected in any of the adenoid ameloblastoma cases. Conclusion: The molecular results support adenoid ameloblastoma as an entity distinct from adenomatoid odontogenic tumor and ameloblastoma. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OL) is the most common oral potentially malignant disorder, with a global prevalence of 2%‐3%, variable malignant transformation rate and incompletely understood aetiology. Considering the subjectivity in oral dysplasia grading, other evaluation methods have been tested as predictors of malignant transformation. DNA ploidy status and loss of heterozygosity signatures have been shown to be good predictive markers of malignant transformation. However, effective markers to predict which lesions will progress to invasive carcinoma and by which mechanisms remain unclear. Recent evidence suggests that dysplasia progression to carcinoma occurs through neutral clonal evolution (i.e. randomly). We focus on the genetic basis of OL, encompassing the gross chromosomal alterations and single‐gene mutations, and discuss such alterations in the context of aetiology, clinical presentation and progression. The deeper we understand the genetic basis of OL, the more we approach a better comprehension of the complex and poorly understood process of oral carcinogenesis. [ABSTRACT FROM AUTHOR]

The article discusses about the study conducted to determine nuclear BAP1 immunoexpression independent of the BRAF V600E status through Ameloblastoma. Topics of discussion includes study was approved by the Ethics Committee of Federal universities of Sergipe and Minas Gerais which concluded that Ameloblastoma reviews the BRAF V600E mutation and melanocytic tumours. Melanocytic lesions presents BRAF V600E positivity and loss of the nuclear expression of tumour suppressor protein BAP1.

Background: BRAF p.V600E is reported in up to 80% of ameloblastomas. Despite the high frequency, the presence of this mutation in different histopathological areas of the tumour has not been investigated. This information has an important role in the use of BRAF p.V600E assessment as an auxiliary tool in the differential diagnosis between unicystic ameloblastoma and other odontogenic cystic lesions, especially when only incisional biopsies are available. Therefore, the purpose of the present study was to investigate BRAF p.V600E heterogeneity in unicystic ameloblastoma. Methods: Five cases of ameloblastoma and two dentigerous cysts were analysed. The regions exhibiting different microscopic characteristics were selected from each ameloblastoma case and manually dissected. TaqMan allele‐specific qPCR or Sanger sequencing was performed to determine BRAF p.V600E status. Results: We screened the mutation in a small cohort of UA and no molecular heterogeneity was found. Four cases of ameloblastoma (80%) exhibited BRAF p.V600E in all different areas evaluated. One case did not harbour the mutation in any microscopic region analysed. The BRAF mutation was absent in the dentigerous cysts. Conclusion: Ameloblastomas appear to exhibit a homogeneous profile regarding the BRAF p.V600E no matter what histological feature is observed under light microscopy, suggesting that this molecular test may contribute to establish the correct diagnosis in cases microscopically resembling other odontogenic lesions. [ABSTRACT FROM AUTHOR]

Objective: Odontogenic keratocyst (OKC) is a benign lesion that tends to recur after surgical treatment. In an attempt to clarify the molecular basis underlining the OKC pathobiology, we aimed to analyze its proteomic profile. Materials and Methods: We compared the proteomic profiles of five OKC and matched normal oral mucosa by using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Then, we performed enrichment analysis and a literature search for the immunoexpression of the proteomics targets. Results: We identified 1,150 proteins and 72 differently expressed proteins (log2 fold change ≥ 1.5; p <.05). Twenty‐seven peptides were exclusively detected in the OKC samples. We found 35 enriched pathways related to cell differentiation and tissue architecture, including keratinocyte differentiation, keratinization, desmosome, and extracellular matrix (ECM) organization and degradation. The immunoexpression information of 11 out of 50 proteins identified in the enriched pathways was obtained. We found the downregulation of four desmosomal proteins (JUP, PKP1, PKP3, and PPL) and upregulation of ECM proteases (MMP‐2, MMP‐9, and cathepsins). Conclusions: Proteomic analysis strengthened the notion that OKC cells have a similar proteomic profile to oral keratinocytes. Contextual investigation of the differentially expressed proteins revealed the deregulation of desmosome proteins and ECM degradation as important alterations in OKC pathobiology. [ABSTRACT FROM AUTHOR]

It has been hypothesized that the human brain has less redundancy than animals, but the structural evidence has not been identified to confirm this claim. Here, we report three redundancy circuits of the commissural pathways in primate brains, namely the orbitofrontal, temporal, and occipital redundancy circuits of the anterior commissure and corpus callosum. Each redundancy circuit has two distinctly separated routes connecting a common pair of cortical regions. We mapped their trajectories in human and rhesus macaque brains using individual and population‐averaged tractography. The dissection results confirmed the existence of these redundancy circuits connecting the orbitofrontal lobe, amygdala, and visual cortex. The volume analysis showed a significant reduction in the orbitofrontal and occipital redundancy circuits of the human brain, whereas the temporal redundancy circuit had a substantial organizational difference between the human and rhesus macaque. Our results support the hypothesis that the human brain has less redundancy in the commissural pathways than that of the rhesus macaque brain. Further studies are needed to explore its neuropathological implications. [ABSTRACT FROM AUTHOR]

Background: Granular cell tumors (GCTs) are rare neuroectodermal soft tissue neoplasms that mainly affect the skin of the upper limbs and trunks and the oral cavity. GCTs are derived from Schwann cells and, ultrastructurally, their intracytoplasmic granules are considered autophagosomes or autophagolysosomes and are consistent with myelin accumulation. Methods: In this study, a convenience set of 22 formalin‐fixed, paraffin‐embedded samples of oral GCTs, all but one sample located at the tongue, was screened for mutations by whole‐exome (WES) or targeted sequencing. Results: WES revealed two novel variants in genes of the vacuolar ATPase (V‐ATPase) complex: ATP6AP1 frameshift c.746_749del, leading to p.P249Hfs*4, and ATP6V1A non‐synonymous c.G868A, leading to p.D290N. Each of these mutations occurred in one case. With regard to the samples that were wild type for these V‐ATPase variants, at least two samples presented variants in genes that are part of endosomal/lysosomal/autophagosomal networks including ABCA8, ABCC6, AGAP3, ATG9A, CTSB, DNAJC13, GALC, NPC1, SLC15A3, SLC31A2, and TMEM104. Conclusion: Although the mechanisms involved in oral GCT initiation and progression remain unclear, our results suggest that oral GCTs have V‐ATPase variants similarly to GCTs from other tissues/organs, and additionally show variants in lysosomes/endosomes/autophagosomal genes. [ABSTRACT FROM AUTHOR]

This paper reflects on the nature of social changes brought about by information and communication technologies for development (ICTD or ICT4D) over the past two decades. We respond to the 2002 Letter to Aunt Ofelia, a publication that resulted from collective workshop of ICTD practitioners in Latin America. The Letter to Aunt Ofelia, written in the form of a letter to an imaginary aunt, presented seven proposals for equitable development using ICT. In this note, we use the epistolary format again as a response from the imaginary aunt, to present 10 challenges that represent failures and setbacks of ICT working against rather than for human development. These challenges pertain to commerce, services, media, surveillance, algorithmic control, addiction, misinformation, acceleration, loneliness, and environmental degradation. These 10 issues deserve our critical attention and creative energies if we are to truly harness the power of ICT for human development with equity, prosperity, and social justice. [ABSTRACT FROM AUTHOR]

Different levels of government often interact on the ground, providing closely related services. While multilevel governance arrangements have been studied broadly, scarce literature has explored the contribution of national governments to achieving subnational policy goals. By reconceptualizing administrative decentralization as coexisting devolution (to subnational governments) and deconcentration (through field units), this research explores the indirect national contribution to subnational performance by delivering associated services. This article tests the following hypotheses: (1) there is a positive effect of national deconcentrated capacity on subnational policy outputs, and (2) under policy overlap, this contribution diminishes with increasing levels of subnational capacity. While Colombian schooling is decentralized, the national government indirectly contributes to education through a national agency that administers child protection services. Analyzing data for Colombian subnational governments over a decade reveals that national capacity boosts education provision while the least endowed regions benefit the most, thus providing evidence supporting both hypotheses. [ABSTRACT FROM AUTHOR]

Tumour metastasis is one of the leading cause of cancer-related mortality. Circulating tumour cells (CTCs) have been implicated in loco-regional and distant metastasis and its role is being extensively studied in various malignancies, including those from the head and neck region. The main challenge in understanding their significance lies in the rarity of these cells in the blood. However, newer technologies have attempted to overcome these pitfalls. This review explores the evolution of CTC research and other related areas, including its biological significance, sustainability within the circulating vascular environment and possible clinical implications. [ABSTRACT FROM AUTHOR]

Aims: Oral and/or oropharyngeal acute mucositis during and after chemo-radiotherapy (chemo-RT) for head and neck squamous cell carcinoma (HNSCC) can be extremely painful, sometimes requiring nasogastric feeding to enable adequate nutrition. The MASCC/ISOO evidence-based guidelines recommend benzydamine mouthwash for mucositis prevention in RT (recently updated to include chemo-RT), and a Cochrane systematic review found other agents to be effective in prophylaxis. Diclofenac mouthwash is licensed for painful oral mucosal inflammatory conditions but to our knowledge has not been assessed in chemo-RT-associated oral mucositis.Method: A clinical observation and service evaluation study in 10 patients undergoing chemo-RT for HNSCC to assess the potential value of diclofenac mouthwash (0.74 mg/mL) in reducing symptoms. Patients used 20ml of mouthwash up to 4 times a day starting in week 3 (of a 6-week course of treatment), recording pain and discomfort scores using a visual analogue scale on days 0, 1,7 and 14 (until the end of week 4). As per our current clinical practice, oral mucositis was not clinically scored as an outcome. Statistical analysis was performed using a one-way ANOVA.Results: Using diclofenac mouthwash, 9/10 patients experienced pain score reduction from day 0 (mean score 6.75 ± SD 1.83) to day 2 (5.05 ± SD 1.62) and day 14 (4.09 ± SD 1.96).Conclusions: Diclofenac mouthwash may be beneficial for managing chemo-RT-induced oral mucositis. While a prospective randomised clinical trial is needed, it can be prescribed for this condition within its current licence. [ABSTRACT FROM AUTHOR]

Background: Brown tumors are giant cell-rich lesions that result from abnormal bone metabolism in hyperparathyroidism, one of the most common endocrine disorders worldwide. Brown tumors occasionally affect the jaws and, despite well-known clinical and microscopic features, their molecular pathogenesis remains unclear. We investigated the presence of pathogenic activating mutations in TRPV4, FGFR1, and KRAS in a cohort of brown tumors since these have recently been reported in giant-cell lesions of the jaws and non-ossifying fibromas of the bones (FGFR1 and KRAS), which are histologic mimics of brown tumors.Methods: We target sequenced 13 brown tumors of the jaws associated with primary or secondary hyperparathyroidism. As mutations in these genes are known to activate the MAPK/ERK signaling pathway, we also assessed the immunostaining of the phosphorylated form of ERK1/2 (pERK1/2) in these lesions.Results: KRAS pathogenic mutations were detected in seven cases (p.G12V n = 4, p.G12D n = 1, p.G13D n = 1, p.A146T n = 1). KRAS variants of unknown significance (VUS), p.A134T and p.E37K, were also detected. All samples showed wild-type sequences for FGFR1 and TRPV4 genes. The activation of the MAPK/ERK signaling pathway was demonstrated by pERK1/2 immunohistochemical positivity of the brown tumors´ mononuclear cells.Conclusion: Mutations in KRAS and activation of the MAPK/ERK signaling pathway were detected in brown tumors of hyperparathyroidism of the jaws, expanding the spectrum of giant cell lesions whose molecular pathogenesis involve RAS signaling. [ABSTRACT FROM AUTHOR]

The forced displacement and transnational migration of millions of people around the world is a growing phenomenon that has been met with increased surveillance and datafication by a variety of actors. Small humanitarian organizations that help irregular migrants in the United States frequently do not have the resources or expertise to fully address the implications of collecting, storing, and using data about the vulnerable populations they serve. As a result, there is a risk that their work could exacerbate the vulnerabilities of the very same migrants they are trying to help. In this study, we propose a conceptual framework for protecting privacy in the context of humanitarian information activities (HIA) with irregular migrants. We draw from a review of the academic literature as well as interviews with individuals affiliated with several US‐based humanitarian organizations, higher education institutions, and nonprofit organizations that provide support to undocumented migrants. We discuss 3 primary issues: (i) HIA present both technological and human risks; (ii) the expectation of privacy self‐management by vulnerable populations is problematic; and (iii) there is a need for robust, actionable, privacy‐related guidelines for HIA. We suggest 5 recommendations to strengthen the privacy protection offered to undocumented migrants and other vulnerable populations. [ABSTRACT FROM AUTHOR]

Electronic cigarettes (e-cigarettes) are a popular method to help quit tobacco smoking. However, there is a paucity of data in the literature on their safety and efficacy. Recently, the Indian Government has called for a ban on all e-cigarettes and taken steps to restrict access to vaping products from the market. This major decision was an attempt to safeguard the younger population from using e-cigarette and their possible longer-term addiction together with its promotions by domestic industries. In this article, we evaluate the role of e-cigarettes to help stop smoking tobacco cessation and consider the factors that have facilitated the ban on e-cigarettes in India. [ABSTRACT FROM AUTHOR]

Autosomal recessive SOPH syndrome was first described in the Yakuts population of Asia by Maksimova et al. in 2010. It arises from biallelic pathogenic variants in the NBAS gene and is characterized by severe postnatal growth retardation, senile facial appearance, small hands and feet, optic atrophy with loss of visual acuity and color vision, and normal intelligence (OMIM #614800). The presence of Pelger‐Hüet anomaly in this disorder led to its name as an acronym for Short stature, Optic nerve atrophy, and Pelger‐Hüet anomaly. Recent publications have further contributed to the characterization of this syndrome through additional phenotype–genotype correlations. We review the clinical features described in these publications and report on a 27‐year‐old woman with dwarfism with osteolysis and multiple skeletal problems, minor anomalies, immunodeficiency, diabetes mellitus, and multiple secondary medical problems. Her condition was considered an unknown autosomal recessive disorder for many years until exome sequencing provided the diagnosis by revealing a founder disease‐causing variant that was compound heterozygous with a novel pathogenic variant in NBAS. Based on the major clinical features of this individual and others reported earlier, a revision of the acronym is warranted to facilitate clinical recognition. [ABSTRACT FROM AUTHOR]

Background and objective: Epigenetic events, as the DNA methylation, may be related to development of inflammatory diseases. Due to the important role of host's response in the pathogenesis of periodontitis, the purpose of the present study was to investigate the methylation profile of genes related to immune response in gingival tissues from patients with generalized periodontitis (GP) compared to healthy individuals. Methods: Gingival tissues were collected from 20 individuals with GP and 20 healthy individuals. Genomic DNA was extracted and submitted to enzymatic digestions. An initial screening using a panel of genes involved with the response immune was performed in pools containing six samples of each group. Genes that presented different levels of methylation between the groups were selected for individual assays for validation. Results: The array results showed an unmethylated profile in the majority of genes evaluated in both groups. MALT1, LTB, and STAT5 genes presented a profile of partial methylation in the control compared with GP group. Validation individual assays using a larger number of samples (n = 20, each group) confirmed the hypomethylation of STAT5 in the GP group compared with control group (P <.001). Conclusion: Generalized periodontitis is associated with hypomethylation of the STAT5 gene. Further studies are necessary to evaluate the functional impact these findings. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of scaffold-mediated localized chemotherapy in cancer.Methods: Databases including PubMed, Cochrane Library, and SCOPUS were searched for articles reporting the use of scaffold-mediated localized drug delivery in cancer. Essential data including scaffold fabrication material and methods, drug dosage and release duration and its effect on the cancer cells were extracted.Results: 15 articles out of 60 screened, fulfilled the eligibility criteria. Among the 15 studies, 5 studies included only cell lines and 2 studies were on mouse models, while 8 studies involved a combination of cell lines and mouse models. Scaffold materials included both synthetic polymers such as poly-lactide, polycaprolactone and natural materials including d-periosteum and human micro-fragmented adipose tissueA wide number of other variables included the fabrication procedure, drugs used, and the methods used to assess the effects on cancer. As a result, it was not possible to make any direct comparison of the efficacy of the therapeutic strategy used in each of these studies.Conclusion: Irrespective of the many variables, a common consensus in all the included studies was that scaffold mediated localized drug delivery effectively reduced cancer cell viability by increasing drug bioavailability to the target tissue, while its localized effect reduced the risk of systemic toxicity. [ABSTRACT FROM AUTHOR]