Mouth Research Articles

Beyond the mouth: An overview of obstructive sleep apnea in adults for dentists.

Obstructive sleep apnea (OSA) is a common and complex medical sleep condition in adults that is associated with chronic medical and mental health conditions. Left undiagnosed and untreated it can decrease quality of life and increase morbidity and mortality. Dentists are at the forefront for screening OSA in their role to maintain the health of the oral cavity. Clinical experience in the management of OSA in dentists is limited. The aim of this article is to provide dentists with foundational knowledge about OSA to empower them to play an active role in the care management of screening and treating OSA.

Metagenomic profiling of plaque microbiota in Indian subjects: identified hidden ecological tapestry.

Dental plaque biofilms are the primary etiologic factor for various chronic oral infectious diseases. In recent years, dental plaque shows enormous potential to know about an individual microbiota. Various microbiome studies of oral cavity from different geographical locations reveals abundance of microbial species. Although, the representation of Indian population in this respect is limited, which make us curious to undergo this study. This study investigates the dental plaque microbiota of North Indian individuals based on their age, gender, and dietary patterns; specifically, food preference and availability of water source using 16S rRNA metagenomics analysis. The findings from this study revealed that Streptococcus levels are high across genders, age groups, and water source, highlighting its role as a predominant dental caries associated species like Streptococcus mutans, Streptococcus pyogenes, Streptococcus sobrinus and Streptococcus oralis in the studied population groups. Additionally, the abundance of Actinomyces is observed higher in young individuals and females whereas Fusobacterium and Leptotrichia were high in elderly individuals. Moreover, non-vegetarians have higher abundance of Streptococcus and Fusobacterium, whereas vegetarians show higher abundance of Prevotella and Leptotrichia. The study also highlights the influence of water type on bacterial composition of dental plaque in the studied population i.e., individuals consuming underground water has high abundance of Streptococcus, whereas individuals consuming RO water exhibit elevated Prevotella and Leptotrichia. Insights emerged from the analysis illuminates the complex dynamics of microbiota in dental plaque among North Indians. This study also highlight that this variation of microbiome is influenced by age, gender, and dietary habits (vegetarian or non-vegetarian lifestyle). These results will fill a significant knowledge gap regarding the Indian dental plaque microbiome but also offer a foundation to conduct metagenome studies and potential therapeutic implications for future personalized oral health interventions.

Thermal stress behavior of monolithic zirconia crowns with different thicknesses.

This study was aimed at investigating the thermal stresses in monolithic zirconia crowns (MZC) of various thicknesses and elucidating their thermal behavior under cooling or heating changes in the oral cavity. Additionally, the clinical availability and potential issues of MZC were examined by comparing them with other crown materials. Finite element models comprising MZC (0.5-, 1.0-, and 1.5-mm thick), cement layers, and abutment teeth were subjected to thermal changes from 37 to 5 °C or 60 °C. Using a thermal distribution at 5 s, the thermal stress was calculated and compared with those of gold alloy and resin composite crowns. The loads corresponding to the thermal stresses were also estimated by comparing them with the stresses induced by vertical loading on the occlusal surface. Tensile stress occurred primarily in the crowns and cement during cooling, whereas compressive stress was generated during heating. Thermal stresses increased from 16.0 to 27.2 MPa with decreasing crown thickness from 1.5 to 0.5 mm and varied with different materials. Although the MZC exhibited the highest thermal stress, the estimated load (200 N) corresponding to the thermal stress was smaller than that of the resin composite (1280 N). Thinner crowns exhibited higher thermal stress, suggesting an increased risk of failure owing to thermal changes. Despite the higher thermal stress in thinner MZC, the stresses were below the fatigue strength of the material, indicating sufficient resistance to thermal changes in the oral cavity.

Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer.

Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer. Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)-negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test. We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm. RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.

Oral lesions and disorders and their prevalence arising from the use of illicit drugs in a prison population.

The dependence on the illicit drugs has been proven to be harmful to the oral cavity and may lead to a series of abnormal manifestations. The main objective of this study was to observe the effects caused by the consumption of illicit drugs in the oral cavity, in a prison population in the North of Portugal. A cross-sectional observational study was conducted involving 91 male inmates aged 25-75 years (mean age 41.14 ± 8.98), from Paços de Ferreira Prison. The participants were subjected to a medical interview and a clinical examination. Descriptive statistics and the Chi-square test were used to assess the association between the qualitative variables. The level of statistical significance used was α ≤ 0.05. The consumption of illicit drugs proved to be a common practice (86.8%), where cannabis, heroin and cocaine were the most prevalent (29.1%). Thirty-one inmates were attending the methadone rehabilitation program (34.1%). Most of patients consuming illicit substances, were also smokers (93.7%) (p<.001). Of the 91 participants, 82 (90.1%) presented oral manifestations, with caries lesions being the most prevalent (61.0%) and oral mucosa lesions the least observed (3.7%). Heavy drug consumption was related with rampant caries lesion (p=.011) and chewing difficulty (p=.024) when compared with cannabis consumption. The main oral manifestations found, associated to the consumption of illicit drugs were caries lesions, tooth loss and sensitivity, periodontal diseases, temporomandibular disorders, xerostomia, and bruxism.

Clinical and Epidemiologic Review of Capnocytophaga Spp. Infections Identified at a Public Health Reference Laboratory-California, 2005-2021.

Capnocytophaga is a genus of bacteria that are commensal to the oral microbiome of humans and some animals. Some Capnocytophaga species are found in the human oral cavity and rarely cause disease in people; the species found in animals are zoönotic and can be transmitted to people via saliva. This study describes the clinical and epidemiologic features of patients from whom Capnocytophaga spp. were isolated from blood and other clinical specimens at the California state Microbial Diseases Laboratory. Clinical information was obtained from laboratory submission forms and any accompanying medical records and/or from matching records in statewide hospital discharge and emergency department databases. During the 17-year study period (2005-2021), Capnocytophaga spp. were isolated in 48 specimens from 47 patients. Capnocytophaga canimorsus, which is a zoönotic species, represented 85% of the Capnocytophaga spp. identified to the species level. The median age was 67 years (range: 30-88 years) for the 42 patients infected with a zoönotic species of Capnocytophaga and 36 years (range: 12-65 years) for the four patients infected with a non-zoönotic species. Twenty-five (60%) patients with zoönotic species infections were male, compared to two (50%) patients with non-zoönotic species infections. Capnocytophaga spp. were most frequently isolated from blood (88%), and the most common case presentation was sepsis (45%). A dog or cat bite prior to diagnosis was reported for 14% of patients infected with a zoönotic species of Capnocytophaga. Records for 45% of patients indicated at least one pre-existing health condition associated with depressed immune function. This study documented that Capnocytophaga spp. can cause rare, severe, invasive disease in mostly older or immunocompromised persons, often without documentation of a dog or cat bite. Providers are encouraged to consider Capnocytophaga spp. infection in immunocompromised pet owners presenting with sepsis, even in the absence of a known animal bite.

Food properties modulate activities in posterior parietal and visual cortex during chewing.

Cross-modal interactions between sensory modalities may be necessary for recognition of chewing food by the invisible oral cavity to avoid damaging the tongue and/or oral mucosa. The present study used functional near-infrared spectroscopy to investigate whether the food properties hardness and size influence activities in the posterior parietal cortex and visual cortex during chewing performance in healthy individuals. It was found that an increase in food hardness enhanced both posterior parietal cortex and visual cortex activities, while an increase in food size enhanced activities in the same regions. These findings suggested a quantitative relationship of oral food properties with activities in the brain regions responsible for object recognition and visuospatial processing. It is thus concluded that heightened neural activities in the posterior parietal cortex and visual area reflect an increased demand for cross-modal representation of food properties related to chewing.

Prognostic significance of diagnosis-to-surgery interval in oral cavity squamous cell carcinoma: A nationwide study.

The question as to whether prolonged diagnosis-to-surgery intervals (DSIs) may compromise survival outcomes in patients with oral cavity squamous cell carcinoma (OCSCC) remains unanswered. This nationwide study was designed to address this issue. We analyzed data from 26,214 patients with first primary OCSCC identified in the Taiwanese Cancer Registry Database between 2011 and 2021. The optimal DSI cutoff was determined based on 5-year disease-specific survival (DSS) and overall survival (OS) rates using Cox regression analysis. Patients were categorized into three distinct DSI groups: ≤20days (47%), 21-31days (31%), and>31days (22%). The 5-year DSS and OS rates for the ≤20/21-31/>31days groups were 81%/78%/77% and 73%/70%/68%, respectively (both p<0.0001). Patients in the ≤20days group had a higher prevalence of pathological stages I-II. After adjustment for potential confounders in multivariable analysis, a DSI>31days (versus≤20days) retained independent associations with adverse outcomes at 5years, with hazard ratios of 1.07 for both DSS and OS. Propensity score matching and multivariable analysis comparing DSI≤20days to DSI>31days stratified by pathological stage III-IV showed that higher DSS and OS rates were observed in patients with DSI≤20days than DSI>31days (68%/66%, p=0.0586; 60%/57%, p=0.0228, respectively), with hazard ratios of 1.09 for both DSS and OS. Our findings indicate that DSI is an independent predictor of 5-year DSS and OS in patients with OCSCC. A DSI exceeding 31days, or even 21days, may potentially decrease survival outcomes.

Unmasking the potential: a historical perspective on the evolution of exfoliative cytology in oral cavity neoplasms.

Exfoliative cytology has proven to be a valuable diagnostic tool in the early detection of malignant neoplasms. However, its application in the oral cavity has been met with skepticism and limited investigation due to the perception that clinical examination alone is sufficient for early diagnosis. Nonetheless, recent research efforts have focused on the utility of exfoliative cytology in oral cavity neoplasms, motivated by the high mortality rate associated with oral cancer. This manuscript reviews the historical development of exfoliative cytology in the oral cavity, highlighting key findings and advancements in the field. Early studies demonstrated the presence of neoplastic cells in oral cavity lesions and emphasized the diagnostic potential of cytology. Subsequent research explored different staining methods and observed the differential reaction of oral cavity cells to radiation therapy. The diagnostic accuracy of exfoliative cytology was reported to be as high as 92%, with a significant number of cases diagnosed as carcinomas without any clinical suspicion. The technique also proved valuable in identifying precancerous and dysplastic lesions and obviating the need for unnecessary biopsies. The manuscript delves into the difficulties encountered in sampling techniques and stresses the significance of appropriate specimen collection and handling. Various staining methods, including Papanicolaou and acridine orange, were utilized for cytological analysis. The manuscript emphasizes the extensive use of exfoliative cytology in oral cavity examinations and stresses the importance of recognizing it as a crucial diagnostic tool. Various studies have reported high positivity rates and the detection of clinically unsuspected malignant lesions. The authors recommend extensive use of exfoliative cytology in routine practice and underscore the necessity of proper sampling and evaluation techniques.

Randomized, Placebo-Controlled, Phase 1 Safety Study of Oral Mucosal Immunotherapy in Peanut Allergic Adults.

Oral Mucosal Immunotherapy (OMIT) uses a specifically formulated toothpaste to deliver allergenic proteins to immunologically active areas of the oral cavity. This represents a new delivery mechanism with several features designed to improve food allergy desensitization. OMIT presents advantages over other approaches to allergy immunotherapy due to its targeted delivery and simplified administration. To determine the safety, tolerability, and adherence of OMIT with INT301 in peanut allergic adults. This Oral Mucosal Escalation Goal Assessment (OMEGA) study enrolled 32 adults, age 18-55, with peanut allergy in a 3:1 ratio to receive either an escalating dose of INT301 or placebo. Entry criteria included a positive SPT with a wheal diameter ≥ 3mm greater than control and/or psIgE ≥ 0.35 kU/L. Subjects were required to fail an oral food challenge ≤ 100 mg dose of peanut protein. Safety and tolerability were monitored during this 48-week trial. 100% of active subjects tolerated the pre-specified protocol highest dose. No moderate nor severe systemic reactions occurred in active participants. Non-systemic adverse reactions were mostly local (oral and nasal cavity), mild and transient. Active subjects adhered to treatment 97% of days on study, with no withdrawals due to study medication. In the OMEGA trial, INT301 met all primary and secondary endpoints of safety, tolerability, and adherence. OMIT appears to be a safe and convenient option for individuals with food allergies. These results support its further evaluation in the pediatric population.

Synthesis and evaluation of the antifungal and antibiofilm potential of aminochalcones.

Candida is a commensal fungus of clinical interest that commonly lives in oral cavity and intestine but can become an opportunist microrganism and cause severe infections. A serie of 10 aminochalcones were designed and synthetized to obtain compounds anti-Candida with potent and broad-spectrum activity. The most active compound J34 demonstrated excellent in vitro activity against Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata and Candida krusei with minimum inhibitory concentration between 1.9 and 7.8µg/mL. The association of aminochalcone J34 with amphotericin B demonstrated synergistic effect against C. albicans, with Fractional Inhibiroty Concentration Index (FICI) value of 0.5. Subinhibitory concentration of J34 inhibited the C. albicans adhesion to human keratinocytes. Treatment with J34 reduced C. albicans biofilm formation, as well as acts on preformed biofilm in concentration-dependent mode. Time-kill curve demonstrated that J34 had fungicidal action after 12h of treatment. Preliminary mechanism of action study showed J34 interacts with membrane ergosterol but does not act on fungal cell wall of C. albicans. In additon, in vivo studies using Galleria mellonella indicated low toxic effect of chalcone J34 after 72h of treatment.

Integrated multi-omics analyses of oral squamous cell carcinoma reveal precision patient stratification and personalized treatment strategies.

Oral cavity squamous cell carcinoma (OSCC), a leading subtype of head and neck cancer, exhibits high global incidence and mortality rates. Despite advancements in surgery and radiochemotherapy, approximately one-third of patients experience relapse. To improve current targeted and immunotherapy strategies for recurrent OSCC, we conducted multi-omics analyses on pretreatment OSCC samples (cohorts 1 and 2, n=137) and identified A3A and EGFR, both at the RNA and protein levels, as inversely expressed markers for patient stratification and response prediction. Survival analysis demonstrated that elevated A3A or PD-L1 expression levels correlated to improved responses to anti-PD-1 therapy in patients (cohort 3a, n=50, IHC). In contrast, high RRAS expression (cohort 4, n=252, qRT-PCR) was significantly associated with OSCC recurrence. Cell-based experiments revealed that RRAS was involved in radiotherapy and cisplatin resistance through the EGFR/RRAS/AKT/ERK signaling pathway. In OSCC patient-derived xenograft (PDX) mouse models, treatments with cisplatin and cetuximab (anti-EGFR) effectively reduced tumor size in EGFR-high-derived (#34) but not A3A-high-derived (#22) PDX tumors. Our study demonstrated that A3A-high tumors were immune-hot and responsive to anti-PD-1 therapy, whereas EGFR-high tumors exhibited chr.7p11.2 gains and DNA repair alterations. Additionally, RRAS-high tumors were associated with OSCC recurrence via AKT and ERK phosphorylation and demonstrate improved clinical outcomes with cetuximab therapy (cohort 3b, n=49, IHC). This study emphasizes the significance of A3A and EGFR expression levels in OSCC patient stratification and precision therapy, suggesting the use of anti-PD-1 or anti-EGFR treatments, respectively based on these biomarkers. Furthermore, RRAS emerges as a novel prognostic marker for local recurrence.

The Influence of Posterior Class II Composite Restoration Location and Techniques on Marginal Sealing.

Background/Objectives: The success of treatment and prevention for secondary caries hinges significantly on the techniques employed in Class II composite restoration. Additionally, the location of the restored tooth within the oral cavity has emerged as a potential factor determining the quality of the restoration. A comprehensive understanding of these interrelated variables is crucial for advancing the efficacy and durability of dental composite restorations. The aim of this study was to assess how various restoration techniques and the specific location of the tooth restoration in the oral cavity affect marginal sealing, verified by the gap created in the tooth-restoration interface. Methods: Sixty extracted human teeth that had been indicated for orthodontic extraction were collected and embedded into a custom-made holder that was located in one of the four quadrants of a laboratory phantom head. Class II resin composite restorations, using flowable and packable composites, were performed on all teeth using two techniques: Pre-cure and Co-cure. The aging of the restored teeth was conducted using cyclic loading and thermocycling. After aging, the teeth were examined under a scanning electron microscope to measure the gap within the tooth-composite interface. Kolmogorov-Smirnov tests were used to assess the data distribution. Unpaired T-tests were employed to compare the mean gaps between the Pre-cure and Co-cure techniques. Additionally, unpaired T-tests were utilized to compare the mean gaps between the mesial and distal parts of the teeth. The Kruskal-Wallis test was used to compare the mean gaps among the four quadrants. The statistical significance was set at p = 0.05. Results: No significant difference in the gaps between the Pre-cure and Co-cure techniques was found (p = 0.212). The tooth's location did not generally affect the restoration's gap interface (p = 0.136). Conclusions: Flowable composites aid in restoring the deep margins of Class II composite restoration. Thus, the potential for further microleakage is similar for both the Pre-cure and Co-cure restoration techniques. The marginal seal of Class II composite restorations is effective when using both Pre-cure and Co-cure techniques, and the restoration site within the oral cavity does not significantly influence the tooth-composite interface seal.

Streptococcus abundance and oral site tropism in humans and non-human primates reflects host and lifestyle differences

The genus Streptococcus is highly diverse and a core member of the primate oral microbiome. Streptococcus species are grouped into at least eight phylogenetically-supported clades, five of which are found almost exclusively in the oral cavity. We explored the dominant Streptococcus phylogenetic clades in samples from multiple oral sites and from ancient and modern-day humans and non-human primates and found that clade dominance is conserved across human oral sites, with most Streptococcus reads assigned to species falling in the Sanguinis or Mitis clades. However, minor differences in the presence and abundance of individual species within each clade differentiated human lifestyles, with loss of S. sinensis appearing to correlate with toothbrushing. Of the non-human primates, only baboons show clade abundance patterns similar to humans, suggesting that a habitat and diet similar to that of early humans may favor the growth of Sanguinis and Mitis clade species.

Medwakh smoking induces alterations in salivary proteins and cytokine expression: a clinical exploratory proteomics investigation

BackgroundMedwakh smoking has radically expanded among youth in the Middle East and around the world. The rising popularity of medwakh/dokha usage is linked to the onset of several chronic illnesses including cardiovascular diseases and cancers. Medwakh smoking is reported to increase the risk of inflammation in the lower respiratory tract owing to oxidative burden. To date, there are no reported studies investigating the impact of medwakh smoking on salivary protein profile. The current study aims to elucidate alterations in the salivary proteome profile of medwakh smokers.MethodsSaliva samples collected from 33 medwakh smokers and 30 non-smokers were subjected to proteomic analysis using UHPLC-ESI-QTOF-MS. Saliva samples were further subjected to validatory experiments involving analysis of inflammatory cytokine profile using LEGENDplex™ Human Essential Immune Response Panel.ResultsStatistical analysis revealed alterations in the abundance of 74 key proteins including immune mediators and inflammatory markers in medwakh smokers (Accession: PXD045901). Proteins involved in building oxidative stress, alterations in cell anchorage, and cell metabolic processes were enhanced in medwakh smokers. Salivary immune response evaluation further validated the proteome findings, revealing significantly higher levels of IL-1β, IL-12p70, IL-23, IFN-γ (Th1 cytokines), IL-6 (Th2 cytokine), and MCP-1 (chemokine) in medwakh smokers. In addition, a substantial increase in abundance of involucrin suggesting a plausible stratified squamous cell differentiation and increased cell lysis in the oral cavity of medwakh smokers akin to chronic obstructive pulmonary diseases (COPD). The protein–metabolite joint pathway analysis further showed significantly enriched differentially expressed proteins and metabolites of glycolysis/gluconeogenesis, pentose phosphate, fructose and mannose, nicotinate and nicotinamide, and glutathione metabolism pathways among medwakh smokers.ConclusionsThe findings of the study provide valuable insights on potential perturbations in various key immune molecules, cytokines, and signaling pathways among medwakh smokers. Medwakh smokers displayed elevated inflammation, increased oxidative stress and defective antioxidant responses, dysregulated energy metabolism, and alterations in proteins related to cell adhesion, migration, differentiation, and proliferation. The findings of study underscore the urgent need for comprehensive public health interventions among youth by raising awareness, implementing effective smoking cessation programs, and promoting healthy lifestyle to safeguard the well-being of individuals and communities worldwide.

Marked Gingival Overgrowth Protruding from the Oral Cavity Due to Sodium Valproate.

Drug-induced gingival overgrowth is associated with various systemic diseases, including epilepsy. Among antiepileptic medications, phenytoin is commonly reported to cause this condition. In contrast, sodium valproate (VPA), another widely used antiepileptic drug, rarely induces gingival overgrowth. This difference in side effects highlights the variability in drug-induced oral complications among different antiepileptic medications. This case study presents a patient who developed significant gingival overgrowth after using VPA for over 10 years. The study aims to identify VPA as the causative agent and observe changes during long-term administration and after dose reduction. Our findings demonstrate that even long-standing gingival overgrowth can improve rapidly following discontinuation of the causative medication, providing valuable insights for managing similar cases in the future.

Assessment of the correlation between the volume of tongue, oral cavity, tongue/oral cavity volume ratio and the upper airway in unilateral cleft subjects: A CBCT study.

The current study was conducted to assess the volume of the tongue, oral cavity, and tongue/oral cavity and their correlation with the volume of the upper airway in cleft subjects compared with the control group. The study population included 60 CBCT images from dental school. The sample comprised 30 unilateral cleft patients and 30 sex and age-matched healthy subjects. The CBCT images were imported to the Mimics software in DICOM format. Then, the segmentation process was done in order to create distinct masks for the upper airway, oral cavity, and tongue. The software calculated the volume of the created masks. The volume of tongue, oral and upper airway were significantly lower in cleft patients than in the control group (P value < 0.05 taken as statistically significant). There was a weak but statistically significant correlation between the U.A.W.V and T.V in both cleft and non-cleft subjects. Additionally, there was a statistically significant correlation between the O.C.V and the U.A.W.V in cleft subjects. Except than the proportion of tongue/oral cavity volume, other volumetric measurements were significantly lower in cleft subjects than control group. This reveals that clefts are not necessarily more susceptible to obstructive sleep apnea. Also, the positive correlation between the volume of the tongue and oral cavity with the upper airway confirms that early expansion of the maxillary region in clefts helps significantly in increasing their upper airway volume.

Dysbiosis-NK Cell Crosstalk in Pancreatic Cancer: Toward a Unified Biomarker Signature for Improved Clinical Outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, primarily due to its immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance. Recent research shows that the microbiome, including microbial communities in the oral cavity, gut, bile duct, and intratumoral environments, plays a key role in PDAC development, with microbial imbalances (dysbiosis) promoting inflammation, cancer progression, therapy resistance, and treatment side effects. Microbial metabolites can also affect immune cells, especially natural killer (NK) cells, which are vital for tumor surveillance, therapy response and treatment-related side effects. Dysbiosis can affect NK cell function, leading to resistance and side effects. We propose that a combined biomarker approach, integrating microbiome composition and NK cell profiles, can help predict treatment resistance and side effects, enabling more personalized therapies. This review examines how dysbiosis contributes to NK cell dysfunction in PDAC and discusses strategies (e.g., antibiotics, probiotics, vaccines) to modulate the microbiome and enhance NK cell function. Targeting dysbiosis could modulate NK cell activity, improve the effectiveness of PDAC treatments, and reduce side effects. However, further research is needed to develop unified NK cell-microbiome interaction-based biomarkers for more precise and effective patient outcomes.

Development and Evaluation of an Automated Multimodal Mobile Detection of Oral Cancer (mDOC) Imaging System to Aid in Risk-based Management of Oral Mucosal Lesions.

Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders associated with an increased risk for oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation. This study reports the development and evaluation of the mobile Detection of Oral Cancer (mDOC) imaging system and an automated algorithm that generates a referral recommendation from mDOC images. mDOC is a smartphone-based autofluorescence and white light imaging tool that captures images of the oral cavity. Data were collected with mDOC from a total of 332 oral sites in a study of 29 healthy volunteers and 120 patients seeking care for an oral mucosal lesion. A multimodal image classification algorithm was developed to generate a recommendation of "Refer" or "Do Not Refer" from mDOC images, using expert clinical referral decision as the ground truth label. A referral algorithm was developed using cross-validation methods on 80% of the dataset, then retrained and evaluated on a separate holdout test set. Referral decisions generated in the holdout test set had a sensitivity of 93.9% and a specificity of 79.3% with respect to expert clinical referral decisions. The mDOC system has the potential to be utilized in community physicians' and dentists' offices to help identify patients who need further evaluation by an oral cancer specialist.

Non-smoking, non-drinking, oral squamous cell carcinoma patients are a distinct and clinically significant group.

Carcinogenesis of oral squamous cell carcinoma (OSCC) has long been associated with exposure to tobacco smoke and alcohol consumption. Some centres have reported that non-smoking non-drinking (NSND) patients represent a significant and increasing proportion of OSCC cases with reports of poorer outcomes. Demographic characteristics are variably reported for this group and carcinogenesis is not fully understood. We present the largest cohort study to date in this subject area and sought to better understand demographics and survival. We interrogated 541 OSCC patients by retrospective analysis to assess risk factor status, disease characteristics and survival. Patients were categorised according to smoking and alcohol exposure with non-smoker (NS) status defined as less than five cigarettes per week with no history of use greater than this. Non-drinker (ND) status was defined as less than three standard drinks per week with no history of alcohol consumption greater than this. Those both NS and ND were categorised as NSND. Subsite, tumour stage and treatment were recorded along with evidence of cervical nodal and distant metastasis. These patients were more likely to be female, older and present with early-stage disease. Tumour site was tongue, maxillary alveolus and buccal mucosa, at variance with the smoker drinker groups. NSNDs comprise a significant proportion our OSCC population. These patients were more likely to be female, older and present with early-stage disease. Tumour site was tongue, maxillary alveolus and buccal mucosa, at variance with the smoker drinker groups. Thus, NSNDs are a clinically distinct and significant group in oral cavity cancer management.