Faculty Bibliography

Cancer pain (CP) arises from a complex interplay between the tumour and its microenvironment. Many patients experience a mixed pain phenotype that encompasses nociceptive, neuropathic and neuroinflammatory mechanisms, and vary across tumour type and disease stage. Despite decades of intensive research, the mainstay of cancer pain treatment is still non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Recent advances in cancer neuroscience have provided novel insights into the neurobiology of cancer pain. The emerging picture of cancer pain is a disorder of aberrant crosstalk between the tumour, the sensory innervation that the tumour creates and the immune cells that these nerves attract. Precision approaches to disrupt this aberrant pain signalling cascade are guided by newly recognized molecular mechanisms. Here, we review the current practice of cancer pain management and the emerging future of personalized, mechanism-driven pain therapy in oncology.

A key aspect of biological studies is the reliance on computation, including the use of mathematical models to mimic the behaviour of cellular functions and networks. Quantitative descriptions of biological processes typically rely on physics and chemistry and thus the generated models are mechanistic e.g. they explain behavior. With some exceptions, such models have been lacking in studies of ameloblasts biology and physiology, in part due to the absence of experimental observations. Here we provide a computational model for Ca²⁺ dynamics in ameloblasts based on recent quantitative data, allowing us to investigate how dynamic forces operate in ameloblasts at the secretory and maturation stages. We simulate the effects of mutations occurring in key Ca²⁺ handling proteins. Finally, we compare how ameloblasts differ from other non-mineralizing cell systems.

Ameloblasts are specialized epithelial cells that form enamel during the secretory and maturation stages, the latter involving an increase in Ca²⁺ transport to mineralize the enamel crystals. During enamel formation, ameloblasts travel several microns while secreting a matrix and are surrounded by several cell layers in the confined space of the enamel organ. Presumably, ameloblasts are subjected to mechanical stimuli e.g. pressure, stretch. Mechanosensitive (MS) or stretch-gated channels are expressed in the membranes of many cells including mineralizing cells. The opening of MS channels occurs in response to physical stimuli and results in the influx of ions. Piezo1 is a non-selective class of MS channel permeable to Ca²⁺ and hence it may contribute to Ca²⁺ homeostasis in ameloblasts. Here we show that secretory and maturation stage ameloblasts express similar protein levels of Piezo1. Cultured rat primary secretory and maturation stage ameloblasts showed stretch-activated currents by patch-clamp. Ameloblasts loaded with the cytosolic Ca²⁺ indicator Fura-2 were also stimulated with the Piezo1-selective activator Yoda1. We show that ameloblasts are sensitive to Piezo1 stimulation which evoked an increase in cytosolic Ca²⁺. This effect was inhibited by Piezo1 blockers. Mechanical analysis of the incisors of Piezo1 cKO mice showed no alterations in hardness or elastic modulus relative to littermate control mice. Our work provides the first evidence that Piezo1 channels are functional in both ameloblast stages and their activation leads to an elevation in cytosolic Ca²⁺, however, Piezo1 does not appear to be essential for enamel mineralization.

Dentistry has witnessed a steady expansion of technological advancements and innovations throughout its history. Today, over 250 names are associated with oral and dental eponyms. In this paper, we highlight 21 eponyms and 24 names that are specific to the field of orthodontics. Each entry briefly presents the individual's name, educational background, notable contribution, and primary references to the original descriptions. This study aims to commemorate these pioneers-many of whom have been forgotten decades or even centuries after their significant contributions to the field.

PURPOSE/OBJECTIVE:To evaluate the mechanical properties of lithium disilicates, and to assess the predictive capability of in silico models for biaxial flexural strength (BFS). MATERIALS AND METHODS/METHODS:] and Weibull modulus [m]. RESULTS:than Vintage Prime and LiSi Press, whereas e.max Press demonstrated similar values to all materials. Vintage Prime demonstrated the highest m among the materials. Similar load-displacement curves from in vitro and in silico BFS were obtained for all materials. CONCLUSIONS:Vintage Prime exhibited higher fracture toughness and m compared to the other materials. The BFS and FEA results were consistent, reinforcing the FEA value as a complementary analytical tool for interpreting material behavior under controlled conditions.

BACKGROUND:Despite the paucity of outcome data, axillary lymph node dissection (ALND) is increasingly being omitted in patients with positive sentinel lymph nodes after neoadjuvant chemotherapy, particularly in those with low-volume residual disease. We investigated oncological outcomes in patients with breast cancer and residual micrometastases in the sentinel lymph nodes treated with or without ALND. METHODS:OPBC-07/microNAC was a retrospective cohort study, using data obtained from the institutional databases of 84 cancer centres in 30 countries. Patients aged 18 years or older with clinical T1-4, N0-3 breast cancer at diagnosis treated with neoadjuvant chemotherapy followed by surgery between Jan 1, 2013, and May 31, 2023, who were found to have residual micrometastases (metastasis measuring >0·2 mm or >200 cells, not exceeding 2·0 mm in size) on frozen section or on final paraffin sections as determined by sentinel lymph node biopsy, targeted axillary dissection (sentinel lymph node biopsy with single or dual-tracer mapping plus image-guided localisation of the initially biopsy-proven and clipped node), or the marking axillary lymph nodes with radioactive iodine seeds (MARI) procedure were eligible for inclusion. The primary endpoint was the 5-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) stratified by type of axillary surgery. Given the median follow-up, here we report 3-year rates and exploratory 5-year estimates. This study was registered with ClinicalTrials.gov, NCT06529302. FINDINGS/RESULTS:1585 female patients with ypN1mi disease were analysed, of whom 804 (50·7%) underwent ALND and 781 (49·3%) did not. Of 1585 women, 238 (15·0%) self-identified as Asian, 65 (4·1%) as Black, 200 (12·6%) as Hispanic, 968 (61·1%) as White, and 114 (7·2%) as unknown race and ethnicity. 925 (58·4%) of 1585 women had cT2 tumours, 1054 (66·5%) were node positive, and 1267 (79·9%) received nodal radiotherapy. The median follow-up was 3·1 years (IQR 1·8-5·2). The 3-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) for the entire cohort was 2·0% (95% CI 1·3-2·9), with no statistical difference identified by extent of axillary surgery. However, patients with triple-negative disease who did not receive ALND had significantly higher rates of any axillary recurrence than women treated with ALND (8·7% [95% CI 4·4-15·0] vs 2·4% [95% CI 0·7-6·5], p=0·018). On multivariable analysis, triple-negative breast cancer (hazard ratio 3·83 [95% CI 1·72-8·52]) and omission of nodal radiotherapy (2·62 [1·19-5·73]) but not omission of ALND (0·86 [0·37-2·00]) were independently associated with an increased risk of any axillary recurrence. INTERPRETATION/CONCLUSIONS:Overall, these results do not support ALND for all patients with ypN1mi on sentinel lymph node biopsy treated with nodal radiotherapy; however, tumour biology should be taken into account when considering ALND omission. FUNDING/BACKGROUND:US National Institutes of Health, National Cancer Institute.

OBJECTIVE:In this study, we aimed to evaluate the effect of an intensive fluoride varnish (FV) regimen on oral microbial communities in children with early childhood caries (ECC). METHODS:Twenty-six children, aged 2 to 5 years, diagnosed with early-stage ECC, were included. They were treated with 5% NaF varnish three times over 2 weeks. Pooled supragingival plaque samples (n = 70) were collected and used for extracting total bacterial DNA. The microbial composition was analyzed using the Human Oral Microbe Identification Next-Generation Sequencing (HOMINGS) method. RESULTS:Analysis of 6172,618 high-quality 16S rRNA amplicons revealed significant changes in the relative abundance of oral microbiome taxa at the phylum level immediately after FV treatment (p = 0.021). Although the relative abundance of several known cariogenic species decreased, none of the shifts were statistically significant at the 1-week visit or persisted at the 2-week visit. At the genus level, children with higher mutans streptococci levels showed higher relative abundance of Bacteroidetes, Firmicutes, and Spirochaetes (p = 0.001, p = 0.023, and p = 0.001), respectively. At the species level, FV treatment significantly increased the relative abundance of Corynebacterium durum (p = 0.009) and Neisseria sicca (p = 0.031) but did not significantly disrupt commensals within the microbial community. CONCLUSIONS:Intensive FV application alone does not significantly alter the core oral microbiome of children with untreated ECC. The treatment may temporarily reduce the cariogenic microbial burden immediately after treatment. However, the long-term effects of FV on the oral microbiome still remain uncertain.

OBJECTIVE:Oral frailty, the age-related decline in oral and pharyngeal function, is associated with physical frailty, sarcopenia, and cognitive decline. The Oral Frailty Index-8 (OFI-8) is a patient-reported outcome measure developed in Japan to assess oral frailty risk. This study aimed to culturally and linguistically adapt the OFI-8 for English-speaking older adults in the United States. STUDY DESIGN/METHODS:Cross-cultural and cross-linguistic adaptation of the OFI-8 by an expert committee, followed by administration of the adapted OFI-8 and structured cognitive interviews with 22 English-speaking adults aged 65 years and older. SETTING/METHODS:Outpatient tertiary academic voice and swallowing center in New York City. METHODS:Following the Professional Society for Health Economics and Outcomes Research (ISPOR) guidelines, the OFI-8 underwent forward translation, back translation, expert committee review, and reconciliation. Cognitive interviews were then conducted with 22 participants aged 65 years and older. A think-aloud and verbal-probing approach was used to evaluate comprehension, clarity, and cultural appropriateness. Interviews were transcribed and analyzed using thematic analysis. RESULTS:Several cultural adaptations were made, including replacing Japanese food examples with US-familiar foods of similar texture. Three questionnaire items and the instructions were refined following participant feedback to improve syntactic flow, clarity, and understanding. The final US-English version maintained conceptual equivalence of the original OFI-8 while adapting language and examples for US cultural relevance. CONCLUSION/CONCLUSIONS:A culturally adapted US-English version of the OFI-8 was developed through structured translation, expert review, and cognitive interviews. Further validation studies are necessary to establish its clinimetric properties and support clinical application for early detection of oral frailty in US older adults.