Search Results (111)

Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD⁺) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, and neurodegenerative diseases. Importantly, SARM1 knockdown or knockout prevents the degeneration; as a result, SARM1 has been attracting attention as a potent therapeutic target. In recent years, the development of several SARM1 inhibitors derived from synthetic chemical compounds has been reported; however, no dietary ingredients with SARM1 inhibitory activity have been identified. Therefore, we here focused on dietary ingredients and found that carnosol, an antioxidant contained in rosemary, inhibits the NAD⁺-cleavage activity of SARM1. Purified carnosol inhibited the enzymatic activity of SARM1 and suppressed neurite degeneration and cell death induced by the anti-cancer medicine vincristine (VCR). Carnosol also inhibited VCR-induced hyperalgesia symptoms, suppressed the loss of intra-epidermal nerve fibers in vivo, and reduced the blood fluid level of phosphorylated neurofilament-H caused by an axonal degeneration event. These results indicate that carnosol has a neuroprotective effect via SARM1 inhibition in addition to its previously known antioxidant effect via NF-E2-related factor 2 and thus suppresses neurotoxin-induced peripheral neuropathy. Full article

Background/Objectives: Invasive pulmonary aspergillosis (IA) is a common infectious disease in patients with hematological diseases. The prevention, early detection, and establishment of treatment strategies for IA are important. The serum galactomannan antigen (GM) mycological test for IA diagnosis, included in the mycology criteria of the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG), is widely used because of its high sensitivity and specificity. However, false-positive results are a concern. Methods: We retrospectively analyzed all GM tests performed at our department in the clinical practice setting between April 2003 and January 2012. Results: Of the 330 cases and 2155 samples analyzed, 540 (25%) were positive (≥0.5). Among the underlying diseases, positivity rates were the highest for multiple myeloma (MM), with 61.3%. By type, positivity rates for IgG, IgA, Bence-Jones protein, and IgD were 71.7%, 33.3%, 57.1%, and 34.6%, respectively. Seventeen out of eighteen cases that were GM-positive at MM diagnosis were false positives, according to the 2008 EORTC/MSG criteria. The IgG and GM values were not directly correlated. Of the seventeen false-positive cases identified, two developed IA during anti-myeloma treatments, and GM values did not become negative during the treatment in most cases. Conclusions: Although subclinical IA may be included in a higher GM index, the results may be prone to false positives; particularly in IgG-type MM, the results should thus be interpreted cautiously. Full article

Background/Objectives: Mean kurtosis (MK) values in simple diffusion kurtosis imaging (SDI)—a type of diffusion kurtosis imaging (DKI)—have been reported to be useful in the diagnosis of head and neck malignancies, for which pre-processing with smoothing filters has been reported to improve the diagnostic accuracy. Multi-parameter analysis using DKI in combination with other image types has recently been reported to improve the diagnostic performance. The purpose of this study was to evaluate the usefulness of machine learning (ML)-based multi-parameter analysis using the MK and apparent diffusion coefficient (ADC) values—which can be acquired simultaneously through SDI—for the differential diagnosis of benign and malignant head and neck tumors, which is important for determining the treatment strategy, as well as examining the usefulness of filter pre-processing. Methods: A total of 32 pathologically diagnosed head and neck tumors were included in the study, and a Gaussian filter was used for image pre-processing. MK and ADC values were extracted from pixels within the tumor area and used as explanatory variables. Five ML algorithms were used to create models for the prediction of tumor status (benign or malignant), which were evaluated through ROC analysis. Results: Bi-parameter analysis with gradient boosting achieved the best diagnostic performance, with an AUC of 0.81. Conclusions: The usefulness of bi-parameter analysis with ML methods for the differential diagnosis of benign and malignant head and neck tumors using SDI data were demonstrated. Full article

Background/Objectives: Deep inspiration breath-hold (DIBH) is a commonly used technique to reduce the mean heart dose (MHD), which is critical for minimizing late cardiac side effects in breast cancer patients undergoing radiation therapy (RT). Although previous studies have explored the potential of machine learning (ML) to predict which patients might benefit from DIBH, none have rigorously assessed ML model performance across various MHD thresholds and parameter settings. This study aims to evaluate the robustness of ML models in predicting the need for DIBH across different clinical scenarios. Methods: Using data from 207 breast cancer patients treated with RT, we developed and tested ML models at three MHD cut-off values (240, 270, and 300 cGy), considering variations in the number of independent variables (three vs. six) and folds in the cross-validation (three, four, and five). Robustness was defined as achieving high F2 scores and low instability in predictive performance. Results: Our findings indicate that the decision tree (DT) model demonstrated consistently high robustness at 240 and 270 cGy, while the random forest model performed optimally at 300 cGy. At 240 cGy, a threshold critical to minimize late cardiac risks, the DT model exhibited stable predictive power, reducing the risk of overestimating DIBH necessity. Conclusions: These results suggest that the DT model, particularly at lower MHD thresholds, may be the most reliable for clinical applications. By providing a tool for targeted DIBH implementation, this model has the potential to enhance patient-specific treatment planning and improve clinical outcomes in RT. Full article

Soft tissue sarcoma (STS) is a rare and heterogeneous disease, which can result in surgeons not considering STS as a differential diagnosis when they encounter a lump. However, unplanned excision (UE) often occurs in nonspecialized sarcoma centers. Before re-excision (RE) after UE, radiological examinations such as magnetic resonance imaging (MRI) should be performed to determine the surgical margin and conduct a pathological evaluation of the UE. However, differentiating between residual tumor and postsurgical changes remains challenging because of the presence of postoperative edema, hematoma, and seroma on MRI. Propensity score matching analysis showed that patients with STS who underwent RE after UE did not have higher mortality or local recurrence rates than those who underwent planned excision (PE), while RE often requires reconstruction procedures. From the patient’s perspective, one operation (PE) is better than two (UE and RE) because it reduces hospital stays and time away from work. Continuous education about STS is necessary for all surgeons to reduce the incidence of UE. Full article

Background/Objectives: Late epilepsy occurring in the late stage after glioblastoma (GBM) resection is suggested to be caused by increased extracellular glutamate (Glu). To elucidate the mechanism underlying postoperative late epilepsy, the present study aimed to investigate the expressions and relations of molecules related to Glu metabolism in tumor tissues from GBM patients and cultured glioma stem-like cells (GSCs). Methods: Expressions of CD44, xCT and excitatory amino acid transporter (EAAT) 2 and extracellular Glu concentration in GBM patients with and without epilepsy were examined and their relationships were analyzed. For the study using GSCs, expressions and relationships of the same molecules were analyzed and the effects of CD44 knock-down on xCT, EAAT2, and Glu were investigated. In addition, the effects of hypoxia on the expressions of these molecules were investigated. Results: Tumor tissues highly expressed CD44 and xCT in the periphery of GBM with epilepsy, whereas no significant difference in EAAT2 expression was seen between groups with and without epilepsy. Extracellular Glu concentration was higher in patients with epilepsy than those without epilepsy. GSCs displayed reciprocal expressions of CD44 and xCT. Concentrations of extracellular Glu coincided with the degree of xCT expression, and CD44 knock-down elevated xCT expression and extracellular Glu concentrations. Hypoxia of 1% O₂ elevated expression of CD44, while 5% O₂ increased xCT and extracellular Glu concentration. Conclusions: Late epilepsy after GBM resection was related to extracellular Glu concentrations that were regulated by reciprocal expression of CD44 and xCT, which were stimulated by differential hypoxia for each molecule. Full article

Advances in genome editing technology have made it possible to create genome-edited (GE) animals, which are useful for identifying isolated genes and producing models of human diseases within a short period of time. The production of GE animals mainly relies on the gene manipulation of pre-implantation embryos, such as fertilized eggs and two-cell embryos, which can usually be achieved by the microinjection of nucleic acids, electroporation in the presence of nucleic acids, or infection with viral vectors, such as adeno-associated viruses. In contrast, GE animals can theoretically be generated by fertilizing ovulated oocytes with GE sperm. However, there are only a few reports showing the successful production of GE animals using GE sperm. Artificial insemination (AI) is an assisted reproduction technology based on the introduction of isolated sperm into the female reproductive tract, such as the uterine horn or oviductal lumen, for the in vivo fertilization of ovulated oocytes. This approach is simpler than the in vitro fertilization-based production of offspring, as the latter always requires an egg transfer to recipient females, which is labor-intensive and time-consuming. In this review, we summarize the various methods for AI reported so far, the history of sperm-mediated gene transfer, a technology to produce genetically engineered animals through in vivo fertilization with sperm carrying exogenous DNA, and finally describe the possibility of AI-mediated creation of GE animals using GE sperm. Full article

Dental cone beam computed tomography (CBCT) is a diverse 3D X-ray imaging technique that has enabled clear visualization of the teeth and surrounding structures. The most common diagnostic purpose of dental CBCT examination in children is ectopic eruption and impacted teeth, and a small field of view (FOV) is often used. Since it is difficult for children to control their body movements, reducing the rotation angle is effective. However, no studies have examined the effects of different rotation angles on radiation doses to highly radiosensitive organs in children using small FOVs. The purpose of this study was to examine the effects of small FOVs (4 × 4 cm and 6 × 6 cm) and rotation angles (360° and 180°) on doses that highly sensitize organs in children using dental CBCT. The entrance surface doses to lenses, thyroid lobes, parotid glands, and sublingual glands of a pediatric whole-body phantom were measured. By reducing the FOV from 6 × 6 cm to 4 × 4 cm, the dose to the sublingual gland could be significantly decreased. Additionally, by reducing the rotation angle from 360° to 180°, the lens dose can be decreased significantly. As the rate of dose reduction varies among organs, it is important to consider the relative positions of different organs with respect to the FOV and the trajectory of the X-ray tube. Full article

Despite advancements in diagnosing and treating non-small cell lung cancer (NSCLC), the prognosis remains poor. Immune checkpoint inhibitors have shown promise in enhancing survival rates. Therefore, this study aimed to investigate the safety of nivolumab administration with concurrent chemoradiation therapy (CCRT) in patients with unresectable locally advanced NSCLC. Twelve patients with unresectable locally advanced NSCLC at Kansai Medical University Hospital and Izumi City General Medical Center were enrolled from May 2018 to September 2020. They received nivolumab (360 mg) tri-weekly twice, weekly carboplatin (AUC 2 min × mg/mL) and paclitaxel (40 mg/m²) for 6 weeks, and thoracic radiotherapy (60 Gy/30 fractions), followed by maintenance nivolumab therapy (360 mg, tri-weekly) for 6 months. The primary endpoint was incidence of dose-limiting toxicities (DLTs), and the secondary endpoints included safety, response rate, progression-free survival (PFS), overall survival (OS), 2-year survival rate, and treatment completion rate. Three patients completed the protocol. Nine discontinued due directly to interstitial pneumonia (three) and pneumonia (one). Ten patients (83.3%) experienced a grade 3 or higher event, of which three (25%) experienced a grade 4 or higher event, and of these, one (8.3%) experienced a grade 5 event. Three patients experienced DLTs. Concurrent nivolumab with CCRT was tolerated in unresectable locally advanced NSCLC, which offers potential treatment benefits. Full article

Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized for their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying their neurotrophic impact on the peripheral nerve system (PNS) remains elusive. Our study delves into the neurotrophic effects of DPP-4 inhibitors, including Diprotin A, linagliptin, and sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), and Stromal cell-derived factor (SDF)-1a—known DPP-4 substrates with neurotrophic properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth in response to these agents. Remarkably, all DPP-4 inhibitors and PACAP demonstrated a significant elongation of neurite length in DRG neurons (PACAP 0.1 μM: 2221 ± 466 μm, control: 1379 ± 420, p < 0.0001), underscoring their potential in nerve regeneration. Conversely, NPY and SDF-1a failed to induce neurite elongation, accentuating the unique neurotrophic properties of DPP-4 inhibition and PACAP. Our findings suggest that the upregulation of PACAP, facilitated by DPP-4 inhibition, plays a pivotal role in promoting neurite elongation within the PNS, presenting a promising avenue for the development of novel DPN therapies with enhanced neurodegenerative capabilities. Full article

Background/Objectives: We examined the frequency of zinc deficiency in patients with Sjögren’s syndrome (SS) and the relationship between zinc deficiency and each of the subjective symptoms and disease activity. Methods: We enrolled 164 patients aged ≥ 20 years with primary SS (pSS) based on the revised diagnostic criteria of the Ministry of Health, Labor and Welfare (1999) and 144 patients with RA diagnosed according to the ACR/EULAR classification criteria for RA (2010) as a comparison group. Subjective symptoms were confirmed using an original questionnaire, and disease activity was determined using the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI). The serum zinc concentrations were measured in both SS and RA patients. Results: The rate of zinc deficiency in the SS group was 26.1%, significantly higher than that in the RA group (7.6%). The rate of zinc deficiency was significantly higher in the pSS group compared with Japanese health checkup recipients reported in the literature. The mean serum zinc concentration in primary SS was 60.6 ± 7.3 µmol/L in the high disease activity group with an ESSDAI of ≥5 points, which was significantly lower than the concentration of 69.7 ± 10.2 µmol/L in patients with an ESSDAI of ≤4 points. Conclusions: The frequency of zinc deficiency was higher in patients with pSS than in patients with RA. Disease activity was also higher in patients with zinc deficiency, suggesting an association between zinc concentration and organ involvement in pSS. Full article

Background/Objectives: An important aspect of the pathophysiology of frailty seems to be the dysregulation of inflammatory pathways and the coagulation system. However, an objective assessment of the impact of frailty on the recovery from surgery is not fully studied. This study sought to assess how frailty affects the recovery of adult spinal deformity (ASD) surgery using blood biomarkers. Methods: 153 consecutive ASD patients (age 64 ± 10 yr, 93% female) who had corrective spine surgery in a single institution and reached 2y f/u were included. The subjects were stratified by frailty using the modified frailty index-11 (robust [R] group or prefrail and frail [F] group). Results of commonly employed laboratory tests at baseline, 1, 3, 7, and 14 post-operative days (POD) were compared. Further comparison was performed in propensity-score matched-39 paired patients between the groups by age, curve type, and baseline alignment. A correlation between HRQOLs, major complications, and biomarkers was performed. Results: Among the propensity-score matched groups, CRP was significantly elevated in the F group at POD1,3(POD1; 5.3 ± 3.1 vs. 7.9 ± 4.7 p = 0.02, POD3; 6.6 ± 4.6 vs. 8.9 ± 5.2 p = 0.02). Transaminase was also elevated in the F group at POD3(ASD: 36 ± 15 vs. 51 ± 58 U/L, p = 0.03, ALT: 32 ± 16 vs. 47 ± 55 U/L, p = 0.04). Interestingly, moderate correlation was observed between transaminase at POD1 and 2 y SRS22 (AST; function r = −0.37, mental health r = −0.39, satisfaction −0.28, total r = −0.40, ALT; function r = −0.37, satisfaction −0.34, total r = −0.39). Conclusions: Frailty affected the serum CRP and transaminase differently following ASD surgery. Transaminase at early POD was correlated with 2 y HRQOLs. These findings support the hypothesis that there is a specific physiological basis to the frailty that is characterized in part by increased inflammation and that these physiological differences persist. Full article

Community co-creation is critical for tackling complex challenges and building a sustainable future, and necessitates collaboration between public and private sectors to co-create value chains. This paper highlights existing frameworks and proposes a heuristic approach that integrates Collective Impact (CI), Social Impact Assessment (SIA), and Community Capital (CC). Through a narrative review, the paper explores how SIA and CC can empower CI by aligning objective data with community context, ensuring solutions that resonate with local needs, promoting equity by fostering inclusive participation and understanding diverse perspectives, and revealing valuable resources within communities and leveraging their strengths for sustainable development. Although the paper delves into roles and responsibilities for each sector involved in co-creation, it acknowledges limitations in areas such as leadership-capacity building for effective collaboration and long-term commitment, impact measurement methodologies that capture nuanced social change over time, and inclusion of diverse participation methods to ensure all voices are heard and represented. By addressing these limitations, the paper calls for further research and development to strengthen community-driven social change. Full article

Background: Our initial clinical study using simple diffusion kurtosis imaging (SDI), which simultaneously produces a diffusion kurtosis image (DKI) and an apparent diffusion coefficient map, confirmed the usefulness of SDI for tumor diagnosis. However, the obtained DKI had noticeable variability in the mean kurtosis (MK) values, which is inherent to SDI. We aimed to improve this variability in SDI by preprocessing with three different filters (Gaussian [G], median [M], and nonlocal mean) of the diffusion-weighted images used for SDI. Methods: The usefulness of filter parameters for diagnosis was examined in basic and clinical studies involving 13 patients with head and neck tumors. Results: The filter parameters, which did not change the median MK value, but reduced the variability and significantly homogenized the MK values in tumor and normal tissues in both basic and clinical studies, were identified. In the receiver operating characteristic curve analysis for distinguishing tumors from normal tissues using MK values, the area under curve values significantly improved from 0.627 without filters to 0.641 with G (σ = 0.5) and 0.638 with M (radius = 0.5). Conclusions: Thus, image pretreatment with G and M for SDI was shown to be useful for improving tumor diagnosis in clinical practice. Full article

Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm³, exercise: 6.4 mm³), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM. Full article