The oral-systemic relationship has long been a focus of vigorous debate. Spanning experimental studies that elucidate underlying mechanisms, critical reviews and advances in data architecture, and clinical and population-based investigations, this editorial highlights the compelling findings presented in this special issue.

Breast cancer is one of the most prevalent malignancies in women globally, characterized by diverse histological and molecular subtypes, each with varying clinical outcomes. Understanding these subtypes and their associated risk factors is critical for accurate diagnosis, prognosis, and treatment planning.

The study scrutinized 187 breast cancer (BC) patients from Hail region of Saudi Arabia, focusing on ABO blood group distribution, histological type, cancer subtype, metastases size, age distribution, body mass index (BMI), gestational diabetes mellitus (GDM) status, and biochemical markers, including plasma calcium, magnesium, and HBA1C levels.

Blood group distribution showed O+ (50.27%) as the most common blood type, followed by A+ (14.97%) and B+ (11.2%). Histologically, Invasive Ductal Carcinoma (IDC) accounts for 64.1% (120) cases, while Triple Negative Breast Cancer (TNBC) con-stitutes 17.1% (32) cases. The most common metastatic sites are the lungs (25.1%) and ax-illary lymph nodes (17.6%). HER2-positive breast cancer, seen in 9.1% of cases, can lead to multi-organ metastases in some cases. Age distribution indicated most patients were 46-55 years old (50 cases), while BMI data exhibited the highest frequency in the obese cate-gory (~90 cases), with 12 having GDM and 177 not having GDM. Calcium levels across age groups slightly fell below the typical adult range (2.1-2.6 mmol/L) with an average of around 2.06 mmol/L. Magnesium levels were elevated in patients less than 35 years of age (7.02 mmol/L) and were low in other groups. HbA1C levels in all age groups ranged from 6.44 to 6.67 mg/dL, aligning with prediabetic or diabetic thresholds. Plasma calcium and magnesium levels were elevated in the weight category, showing slight deviations from the normal range. Underweight patients displayed the lowest HbA1C levels with all weight cat-egories exceeding 6.5 mg/dL, indicating diabetes.

The results highlight IDC as a predominant BC type, with O+ as the most common blood group among patients. TNBC remains a treatment challenge due to a lack of hormone receptors. Metastases mainly affect the lungs and lymph nodes. Elevated BMI, calcium, and magnesium levels correlate with increased HbA1C, suggesting a diabetic link. Emphasizing personalized treatment, obesity management, and electrolyte monitoring., the present research advocates a holistic approach for improved BC outcomes and suggests fu-ture exploration of metabolic influences.

To investigate the endocannabinoid system (ECS) and affective state responses to acute aerobic exercise in adult cancer patients versus their healthy peers.

Participants engaged in 30 min of quiet rest followed by 30 min of exercise. Exercise involved 5-min warm-up/cool-down procedures and 20 min of moderate-intensity training (64-76% of age-predicted maximal heart rate) on a treadmill or cycle. Blood samples and 10 Visual Analog Scales (VAS) were collected before and after each condition. Participants were also asked after exercise: 'Did you experience a Runner's high'. Blood samples were analysed for endocannabinoids: N-arachidonoylethanolamine (AEA; anandamide), 2-arachidonoylglycerol (2-AG) and 1-arachidonoylglycerol (1-AG), and endocannabinoid-like lipid mediators: palmitoylethanolamide (PEA), oleoylethanolamide (OEA) and stearoylethanolamide (SEA).

Cancer patients had lower circulating AEA, OEA and log SEA versus controls across all timepoints (all p < 0.06). In the total cohort, exercise increased AEA, log 1-AG, OEA, PEA and log SEA (all p = 0.05) while log 2-AG did not change. Of 10 VAS, only Happiness increased with exercise in the total cohort (p = 0.02). There were no group x time effects or associations between ECS and VAS responses to exercise. Five patients per group (50%) reported experiencing a Runner's high.

Exercise increased endocannabinoids and endocannabinoid-like lipid mediators in the total cohort. However, cancer patients exhibited lower AEA, OEA and SEA concentrations versus their peers, indicating potential ECS dysfunction. Additional research is required to investigate the effect of various modalities and dosages of exercise on ECS markers and the clinical interpretation of these adaptations across a range of cancer populations.

Australian New Zealand Clinical Trials Registry #: ACTRN12623000193673.

Healthy tissue toxicity is the main limitation for the treatment of brain tumors using radiotherapy (RT). Megavoltage X-ray Minibeam Radiation Therapy (MBRT) and proton Minibeam Radiation Therapy (pMBRT) are novel therapeutic approaches demonstrated to reduce healthy tissue toxicity, enhancing the therapeutic possibilities of challenging cases. Owing to the different radiation types delivering the dose, their dosimetric properties may make one approach more suitable than the other depending on tumor type and location. While both techniques have been extensively studied in small animal models, canine clinical studies provide a closer approximation to human conditions.

This study aims to compare the dosimetric performance of MBRT and pMBRT in canine brain tumors and to determine which modality provides more favorable dose distributions depending on tumor location.

Three representative cases were chosen, and MBRT and pMBRT treatments for a prescribed dose of 26 Gy to the planning target volume (PTV) were simulated using Monte Carlo methods. The in-depth evolution of the minibeam patterns was investigated for both modalities. The dose distributions within the PTV, healthy brain and surrounding tissues evaluated by calculating and comparing the corresponding peak, valley, and mean doses.

pMBRT achieves dosimetric superiority for tumors in the rostral cerebrum surrounded by highly heterogeneous tissue with one entry port. MBRT achieves optimal dose distributions in a two-beam configuration for deeper and more centered targets, where the reduced lateral spread of X-ray minibeams preserved dose heterogeneity.

In this dosimetric comparison of MBRT and pMBRT for the treatment of spontaneous canine brain tumors, the distinct in-depth physical behavior of X-ray and proton minibeams makes each modality more suitable for specific target locations to achieve optimal dose distributions. These findings provide valuable guidance for future veterinary clinical trials and represent an important step toward the clinical implementation of MBRT and pMBRT.

The tumor-associated autoantibody against senescence marker protein-30 (SMP30) serves as a critical serum biomarker for the early detection of hepatocellular carcinoma (HCC), enabling rapid and non-invasive cancer diagnosis and monitoring. However, the accurate detection of the SMP30 antibody remains challenging due to the complex composition of blood and the heterogeneity of circulating antibodies. This study introduces a highly sensitive and straightforward method for SMP30 antibody detection, utilizing a graphene oxide-Hemin (GO-Hemin) composite nano-mimetic enzyme in combination with ferrocenyl-tyramine (Fc-Tyr)-mediated tyramine signal amplification (TSA) within microtiter wells. A solid-phase protein with high affinity selectively captures the SMP30 antibody, while the target is identified via nano-mimetic enzyme labeling of a secondary antibody. The subsequent nano-enzymatic reaction facilitates the deposition of Fc-Tyr, generating a strong electrochemical signal. The biosensor achieves high sensitivity through enhanced electrochemical transduction and minimal spatial resistance at the electrode interface. By integrating immunocapture specificity with electrochemical amplification, this approach enables high-throughput analysis in clinical applications. Experimental results demonstrate that this biosensor can detect smp30 antibodies at concentrations as low as 0.1086 ng/mL, with a detection range spanning 0.1 ng/mL to 1 μg/mL. Analysis of authentic serum samples confirmed that when combined with ELISA, the sensor accurately measured SMP30 antibody levels in serum samples from clinical hepatocellular carcinoma patients. The results demonstrated consistent detection outcomes with recovery rates ranging from 93 % to 104 % and relative standard deviations (RSD) between 1.2 % and 3.7 %. This platform provides a practical and efficient tool for detecting SMP30 antibodies and holds broader application potential in tumor marker monitoring and cancer diagnosis.

Despite the growing need for palliative care, limited evidence exists on Moroccan nurses' knowledge and perceptions in this field, representing a critical gap that may affect the quality of patient care. Addressing this gap is essential to ensure effective palliative care delivery. Therefore, this study aimed to assess Moroccan nurses' knowledge and perceptions of palliative care and to identify factors influencing their competencies in this area.

A cross-sectional analytical study was conducted among Moroccan nurses between April 2023 and April 2024. An anonymized online questionnaire (Palliative Care Quiz for Nursing) was distributed. Data were analyzed using descriptive and inferential statistics with R/RStudio and Excel software.

A total of 480 nurses participated in the study. Overall, nurses demonstrated limited knowledge of palliative care, with a mean score of 5.6/20, corresponding to a 28.53 % correct response rate, particularly low in the psychological and spiritual dimensions. Independent predictors of a higher level of knowledge included male gender (OR = 5.46, p < 0.001), professional experience exceeding 16 years (OR = 2.12, p = 0.001), and training in oncology or palliative care (OR = 3.53, p = 0.006).

The study reveals a low level of palliative care knowledge among nurses in Morocco, despite institutional efforts. It recommends the early integration of palliative care into health systems, the development of multidisciplinary teams, access to essential medications, and the creation of educational programs tailored to low-resource settings.

Genetically modified cell-based therapies hold transformative potential, particularly for patients with rare cancers and ultra-rare diseases. However, progress toward regulatory approval, reimbursement, and broad patient access is often constrained by misaligned regulatory, manufacturing, and financial frameworks that do not reflect the realities of treating small populations and low-throughput production models. Drawing on a collaborative white paper and public meeting convened by Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy in May 2025, this commentary outlines three strategies to streamline regulatory pathways and enable timely, sustainable access: (1) flexible approaches to Chemistry, Manufacturing, and Controls requirements in small populations, (2) adaptable regulatory frameworks to support diverse manufacturing models, and (3) limited cost recovery mechanisms to bridge early access and development gaps. Recent regulatory and policy discussions have echoed these priorities, signaling an opportunity to align oversight with operational realities to advance innovation and access for patients in high-need settings.

Objective: To evaluate clinical outcomes of occlusion-guided vascularized folded fibula flap reconstruction with delayed implant restoration for mandibular defects after benign tumor resection. Methods: A total of 12 patients with benign mandibular tumors underwent free folded fibula flap reconstruction at the First Affiliated Hospital of Bengbu Medical University between January 2020 and December 2023, including 7 males and 5 females, aged 21-52 years. Six months after mandibular reconstruction, the internal fixation titanium plates were removed, and dental implants were placed using a preoperatively fabricated occlusal guide, followed by second-stage implant surgery and prosthetic restoration. Mandibular CT scans were obtained 6 months after reconstruction to compare the fitting accuracy between the preoperative virtual design and the actual reconstructed mandible. The implant stability quotient (ISQ) was measured 3 months after implant placement. Masticatory efficiency and Enneking lower limb function scores were evaluated at the following time points: before tumor surgery (T1), before implant placement (T2), 6 months (T3) and 9 months (T4) after implant crown restoration. One-way repeated measures ANOVA was used to analyze the masticatory efficiency and lower limb function scores. Results: The free folded fibula grafts were successfully performed via an intraoral approach in all 12 patients, with a 100% of survival rate. Mandibular defects included Brown class I in 6 cases, class II in 2 cases, and class III in 4 cases. A total of 42 implants were placed with successful osseointegration. The ISQ measured at 3 months post-placement was 64.10±4.18. At 6 months postoperatively, morphological analysis comparing the preoperative virtual surgical design with the actual postoperative reconstructed mandible revealed a reconstruction accuracy of 84.27%±4.23%. Significant differences were observed in Enneking scores and masticatory efficiency across all four time points (all P<0.001). Masticatory function showed significant improvement at T4 compared that at T2 [(88.06±3.66)% vs. (65.44±3.82)%, P<0.05]. Conclusion: Occlusal function-guided mandibular reconstruction with vascularized folded fibula flap after removal of benign mandibular tumors is a reliable method, which is associated with minimal donor-site morbidity and enables patients to restore precise occlusion and to achieve favorable masticatory efficiency.