Pyroptosis and Oral Cancer.

Cell death is a basic biological occurrence which is required for the existence and growth of an organism.1 Programmed cell death sustains tissue homeostasis facilitating the elimination of redundant cells.2 When an infectious disease sets in, cells that have been infected by pathogens prove harmful to the host eclls.2 Evidence has proved that cell death has a role in immune defense against infectious diseases.1 Cell death can be broadly classified based on its initiating events, such as apoptosis, pyroptosis and oncosis.

A Critical Appraisal on the "Level-of-evidence" Classification Systems.

Evidence-based medicine is about analyzing the evidence and then utilizing the same analysis in making clinical decisions. The key element of evidence-based medicine is the hierarchical system of categorizing evidence. This hierarchy is known as the "levels of evidence".1 Clinicians use this classification to identify the highest level of evidence to answer clinical questions. Various types of research studies answer the different kinds of clinical questions.1.

Bibliometric analysis of highly cited papers on oral mucosal lesions in COVID-19: Trends and impact in medical literature.

Objective: Bibliometric analysis of highly cited papers facilitates researchers in formulating strategic research possibilities and addressing gaps in specific domains. In this context, a bibliometric analysis was conducted to identify published papers on "oral mucosal lesions in COVID-19" within medical literature. Methods: A comprehensive search was performed in the Scopus database in July 2023. Relevant articles were retrieved, reviewed, and data for the bibliometric analysis was recorded. Network visualization of authors, countries, and keywords was generated using VOSviewer software. Results: The analyzed articles were published over the last three years, from 2020 to 2023, with the highest output observed in 2021. The citation count for individual papers ranged from 1 to 340, with a mean of 22.325 ± 58.93 citations. A total of 37 journals were involved in publishing papers on this topic, and five authors each contributed three papers. Notably, Brazil made the highest number of contributions with eight papers. Among the 40 papers, 19 were review papers and 16 were articles discussing various aspects of oral mucosal lesions in COVID-19 patients. Additionally, six papers were identified as systematic reviews, designated with a high level of evidence. Conclusions: This study presents a comprehensive bibliometric analysis of papers published on "oral mucosal lesions in COVID-19." The findings will assist researchers in identifying impactful papers, understanding the prevailing research trends, and guiding future research directions in this domain. The insights gained from this analysis can contribute significantly to advancing knowledge and improving patient care in this critical area of study.

Tumor infiltrating neutrophil microabscess in OSCC: A poorly understood histopathologic prognosticator.

OBJECTIVE: Role of neutrophils in shaping the tumor microenvironment is well known in oral squamous cell carcinoma (OSCC). However, neutrophil microabscess (NM) formation within the tumor islands is distinctive phenomenon and has never been investigated in the literature. This pilot observational study identifies the incidence of NM in OSCC and its clinicopathologic correlation as a platform for the future studies. METHODOLOGY: A retrospective study was carried out on archival specimens of 121 cases of surgically excised OSCC specimens for identification of NM formations within the tumor islands using compound microscope. Mean NM density was calculated based on the quantification done at five randomly selected hotspots. RESULTS: Out of total 121 cases of OSCC, thirteen (10.74%) cases showed a frank evidence of NM within tumor islands. The hotspot analysis showed that the NM density ranges from 2 to 7 with mean of 3.76 ± 1.39 per high power field. NM density was higher in moderately differentiated OSCC (3.76 ± 1.93) than well differentiated (3.76 ± 1.93) however the differences were not statistically significant (p = 0.165). Similarly, higher NM density was reported in advanced T stage, lymph node involvement, advanced TNM stage and lymphovascular invasion, however, the results were statistically insignificant. CONCLUSION: There is evidence of NM formation in the tumor islands of OSCC, however their exact role as a prognosticator needs further exploration with large sample size and follow-up data.

Force, alternate movements, snap, suction and vibration functions of tongue are altered in oral submucous fibrosis patients.

Background: One of the most common clinical manifestations of oral submucous fibrosis (OSMF) is restricted tongue movements. However, the characterization of involvement is needed to better understand the impairment of its functioning. In the present study, force, alternate movements, snap, suction, and vibration functions of the tongue were investigated in OSMF patients. Methods: A total of 53 OSMF and 40 healthy individuals were recruited in the present study. Clinical parameters were used for the diagnosis and grading of OSMF. Alternate movements, snap, suction, vibration of the tongue and tongue force were assessed using standard methodology. Results: Out of 53 OSMF subjects, 22 (42%) were in early stages and 31 (58%) in late stages. There were statistically significant differences between the OSMF and healthy individuals for tongue functions such as protrusion, retraction, lateral movements, altered snap, suction, and tongue vibration (p < 0.00001). All of the aforementioned tongue functions were more affected in advanced stage OSMF than in early stage OSMF (p < 0.00001). Conclusion: Force, alternate movements, snap, suction and vibration functions of tongue are significantly altered in OSMF patients. The performance of the tongue movements by the OSMF subjects worsened with the disease progression.

Clinico-pathological and prognostic overview of metastasizing ameloblastoma: An overview of the systematic reviews.

Background: Metastasizing Ameloblastoma (MA) is an aggressive variant of ameloblastoma (AM) with the ability to metastasize without cytological malignant changes. Thus it aims to comprehensively review the clinico-pathological and prognostic aspects of MA through integration of current literature. Methods: Electronic searches were conducted in PubMed-MEDLINE, Scopus, Web of Science and Google Scholar. Two independent reviewers screened abstracts and evaluated paper eligibility. AMSTAR2 checklist was used to assessed methodological quality of included systematic reviews (SRs). Results: From 390 initial papers, 279 underwent eligibility screening, with five systematic reviews (SRs) meeting inclusion criteria. Six hundred sixty-one MA cases were found in five SRs that were included. MA predominantly affects men, exhibits mandible preference, and occurs in individuals in their fourth or fifth decade. Benign metastatic deposits commonly manifest in lungs and lymph nodes. Distant metastasis probability rises with multiple recurrences and incomplete surgical removal. Tumor recurrence and metastasis unfavorably impact clinical outcomes. Quality of evidence assessment was absent across SRs; four SRs were critically low in methodological quality. Conclusions: AM's metastatic potential lacks predictability. Early/multiple recurrences post-treatment may signal poor prognosis, warranting vigilant follow-up. Methodical analysis of each AM case is imperative to comprehend the metastatic-benign histology relationship.

Unexpected additional pathologies at the surgical margins of oral squamous cell carcinoma.

Background: There is a scarcity of literature on the presence of additional unexpected pathologies at the surgical margins of oral squamous cell carcinoma (OSCC). It is quite possible that such pathologies might get overlooked because of primary focus on the malignancy at the surgical margins. With this view in mind, a retrospective observational study has been designed to re-visit the surgical margins of OSCC for the possible presence of unexpected pathologies. Methods: Haematoxylin and eosin-stained sections of 96 cases (four surgical margins in each case) of OSCC were carefully examined under a compound microscope by two oral pathologists for the presence of any additional pathology. Results: Out of 96 specimens of OSCC, 76 (79.2%) cases showed the presence of accidental pathologies. The surgical margins of 20 (20.8%) cases showed no evidence of any pathology, whereas the margins of 23 (23.95%) cases were associated with more than one pathology. The most commonly observed accidental pathology was oral submucous fibrosis (40.625%), followed by leukoedema (16.675%), retention cysts (10.42%), and calcifications (7.3%). The mucous extravasation phenomenon (6.25%), minor salivary gland (MSG) inflammation (6.25%), and lichen planus (5.21%) were also observed in the surgical margins of OSCC. Conclusion: A significant number of accidental pathologies exist at the surgical margins of OSCC. This effect could be because of over-emphasis on the tumour status at the surgical margins, which leads to over-looking of minor pathologies.

Scarcity of publicly available oral cancer image datasets for machine learning research.

Publicly available image datasets of pathologies have easy accessibility and thus, are increasingly being used in the field of machine learning and medical diagnosis. As oral cancer is the most common head and neck cancer with an increasing incidence rate, it is of paramount importance to know the status of publicly available datasets. We designed a systematic search (PubMed, Google Scholar, Google Dataset Search, and Google) to identify the publicly available oral cancer image datasets. After carefully screening 332 articles/datasets, only one met the selection criteria and was available publicly. However, it contained images of cancerous lesions of only lips and tongue. This first-of-its-kind analysis made realize a dire need for publicly available datasets in oral cancer. It will help researchers in the development of effective machine learning algorithms for oral cancer.

Viral cytopathic effect in maxillary sinus epithelium and SARS-CoV-2: Pitfalls in diagnostic characterization.

Viral cytopathic effects (VCE) are a well-known phenomenon associated with SARS-CoV-2 infection, especially in the cells associated with the lungs. Because maxillary sinus epithelium expresses angiotensin-converting enzyme 2, cells associated with it are more likely to become infected with SARS-CoV-2 and develop VCE. If VCE is seen in with background of a confirmatory COVID-19 diagnosis, then connecting both become quite convincing. However, the diagnostic problem is expected when a similar VCE is seen without any confirmatory diagnosis of CODIV-19. We reported a biopsy sample of maxillary sinusitis in a COVID-19 negative patient. Histopathological examination revealed a pathognomonic VCE in the localized proliferating pseudostratified ciliated epithelium. The only confirmatory aspect linking this VCE with the SARS-CoV-2 was the detection of virus particles at the tissue level. In the present paper, pitfalls and recommendations for future research on this topic are discussed.

COVID-19 and oral cancer: Critical viewpoint.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has marked the beginning of a new pandemic named coronavirus disease 2019 (COVID-19). The World Health Organization has announced it as a health emergency that is of international concern. The disease has been reported to cause respiratory illness, pneumonia and even hinder the immunity of an individual. Individuals with disturbed immune responses have been found to be quite susceptible to this viral infection. Oral cancer patients are also at high risk in this pandemic situation and might encounter severe detrimental outcomes. Angiotensin receptors, documented in studies as the path of entry of this virus, are highly expressed in the epithelial cells of oral mucosa, making the group of individuals with oral cancers even more vulnerable. Extracellular matrix metalloproteinase inducer is another potential target for SARS-CoV-2. An exhaustion of angiotensin converting enzyme 2 cell receptors leads to protumoral effects, whereas a downregulation of extracellular matrix metalloproteinase inducer leads to antitumoral effects. Thus, it causes a variation of the biological behavior of the tumor. This article focusses on the molecular mechanisms, effects and patho-physiology of COVID-19 in oral squamous cell carcinoma patients. The different molecular changes in oral squamous cell carcinoma in the background of COVID-19 will modify various environmental factors for this pathology and have an effect on the carcinogenesis process. Understanding the behavior of the tumor will help plan advanced treatment strategies for oral squamous cell carcinoma patients in the background of COVID-19.

Professional science education videos improve student performance in nonmajor and intermediate biology laboratory courses.

Undergraduate biology laboratories emphasize hands-on skills. Typically, descriptions of manual techniques are delivered via written instruction. Custom-produced prelab instructional videos, which augment prelab instruction, have come into wider use in recent years. However, institutional and economic barriers can interfere with video production at all colleges and universities. In such cases, professionally produced laboratory instructional videos provide an attractive alternative. We hypothesized that students who watch short, professionally produced instructional videos before performing a laboratory would feel more confident and achieve greater learning gains than students whose prelab instruction was limited to handouts. For this proof of concept study, we investigated the value added when students watched a brief video, twice per lab, in an intermediate molecular biology course at a small, liberal arts university, and in a nonmajors biology course at a large, public research university. Both video and nonvideo comparison groups were administered a pre- and postlab exams. A postlab self-efficacy survey was also administered to video groups. Our results reveal that in three out of the four laboratory classes, students who watched professional instruction videos performed significantly better in both pre- and postlab exams. For these students, we observed up to a two-fold increase in test scores on scientific concepts and techniques. For all classes, most of the video group students reported that the video contributed to their confidence, comprehension of concepts, and understanding of how to conduct the lab. We conclude that professional instructional videos may address production barriers and have the potential to effectively enhance undergraduate science curricula and significantly improve students' performance.

Readdressing dysplasia at surgical margins as predictive biomarker of malignant transformation.

Clinical, histological and molecular alterations observed at surgical margins could be regarded as predictive markers of malignant transformation. However, there are contrasting views on usefulness of oral epithelial dysplasia (OED) in predicting malignant transformation. In this regard, investigation of OED status at surgical margins could give an interesting perspective to this notion. We searched the reputed databases to retrieve the original research articles wherein the OED status was investigated at the mucosal surgical margins of oral squamous cell carcinoma (OSCC). Intriguingly, in all the studies, number of cases in 'no dysplasia' category was higher than other grades of dysplasia. In our institutional experience of 92 cases of OSCC, 75 (82%) cases showed no evidence of dysplasia at surgical margins. Thus, we conclude that dysplasia status at surgical margins does not support the OED as potential marker of malignant transformation.

Conspicuous and frank dilated vascular spaces: A marker of malignant transformation in oral submucous fibrosis.

Histo-morphological alterations observed at mucosal surgical margins can be envisaged as potential markers of malignant transformation. In this paper, we have presented a very striking observation at the mucosal surgical margins of oral squamous cell carcinoma arising in the background of oral submucous fibrosis (OSCC-OSMF). Out of 38 cases of OSCC-OSMF, 22 (57.89%) showed conspicuous large dilated vascular spaces lined by endothelial cells in the background of dense fibrosis. These large dilated areas were engorged with red blood cells and were located at the juxta-epithelial and submucosal regions. Since surgical margin tissues are biologically close to malignant transformation, we proposed this unique feature as a potential predictive marker for oral submucous fibrosis that will aid in the early detection of OSCC. Future cohort studies are warranted to prove the authenticity of the present observations.

Hemorrhagic areas as a histological prognosticator in oral cancer: A novel proposition.

Determination of prognosis in oncology practice is a major challenge and many histological prognosticators have been applied because of the ease and simplicity of using them in day-to-day practice. Our histopathologic observation on 96 oral squamous cell carcinoma (OSCC) specimens revealed 34 cases associated with frank hemorrhagic areas, which were close to tumor cells. Hence, we propose that there could be a cross-talk between tumor cells and RBCs which can modulate the biological behavior of the tumor and prognosis of the patient. In the present paper, a scientific foundation is provided for this proposition. Furthermore, an experimental approach is recommended which will facilitate the identification of extracellular metabolites within the tumor microenvironment near RBCs. Such studies may pave the way for a better understanding of the clinical heterogeneity of oral cancer due to differential heme content of red blood cells (RBCs) in the tumor microenvironment (TME).

Denture induced mechanotransduction can contribute to oral carcinogenesis.

Mechanical stresses in the form of substrate rigidity, hydrostatic pressure, compressive, tensile and shear stress has been regarded as an important motive for the epithelial carcinogenesis brought about by the activation of Hippo signaling pathways. Masticatory forces generated in edentulous patients with dentures are transferred directly to the palatal mucosa (maxillary denture) and alveolar mucosa (mandibular denture). Thus, the oral mucosa present underneath the dentures experiences compressive, shear and tensile stresses on a day-to-day basis. These stresses can induce carcinogenesis by mechano-transduction and subsequent activation of numerous carcinogenesis relevant signaling pathways such as the HIPPO pathway. With this contention in mind, we proposed a hypothesis, which explains the pathogenesis for the presence of oral squamous cell carcinoma in denture wearer patients. Efforts were made to envisage the appropriate experimentations for the evaluation of the hypothesis. As a therapeutic implication, flexible dentures, soft denture, or medicated dentures could be prescribed for the high-risk groups having potentially malignant lesions in the oral cavity.