Mental health encompasses subjective well-being (SWB) as well as psychopathology (PP). SWB and PP are related but separate domains: some individuals experience high SWB despite high PP, and others experience low SWB despite minimal PP. Given substantial and heterogeneous developmental changes in both domains during adolescence, examining their co-developmental trajectories may clarify how they integrate across this period. Using data from the Tokyo Teen Cohort (N = 2994), a population-based prospective birth cohort study, we conducted parallel process latent class growth analysis to cluster SWB-PP trajectories at ages 10, 12, 14, and 16 years. We then investigated various sociodemographic, individual, familial, and socioenvironmental correlates for each class. We identified four distinct classes: high SWB-low PP (55.0%), high SWB-mid PP (20.2%), low SWB-mid PP (17.0%), and mid SWB-high PP (7.7%). SWB declined from ages 10 to 16 years across all four classes. Lower PP did not necessarily correspond to higher SWB, and in some pairs of classes, the relationship between SWB and PP levels was reversed. When comparing the two classes with moderate PP, higher aspirations, more prosocial behavior, and better interpersonal relationships were associated with the high SWB class. In contrast, being female and having a higher household income were associated with the low SWB class. Discrepant SWB-PP trajectories suggest characteristic patterns of developmental integration between these domains during adolescence. Considering their interplay may complement domain-specific approaches and inform psychosocial supports aimed at maintaining SWB even in the presence of PP.
The relationship between the behavior of inhaled particulate matter and the inflammatory response in the lungs is not clear. In the present study, we investigated the localization of Asian sand dust (ASD) particles intratracheally instilled into the lungs and the responded activation of NF-κB. One hour after intratracheal ASD administration, quantitative analysis of NF-κB in the nuclei of lung tissues, translocation of NF-κB protein, and ASD localization were examined by enzyme-linked immunosorbent assay, immunohistochemistry (bright field), dark field observation, and Raman technique. ASD exposure induced the nuclear translocation of NF-κB in type II alveolar epithelial cells, alveolar macrophages, and neutrophils within the alveolar wall. Dark field observation and Raman analyses revealed that the ASD components Fe2O3, TiO2, and SiO2 were detected in or near these cells in which immunoreactive NF-κB was present. These results indicate that this combined technique, which takes advantage of Raman spectroscopy, may better evaluate the spatial relationship between the localization of particulate matter and the organ's early inflammatory response.
Limited evidence is available regarding rates of vascular events and mortality associated with an initial and a recurrent ischaemic stroke (IS) in people with non-cardioembolic IS (NCIS). This study evaluated rates of clinical events and antithrombotic therapy among people with NCIS or transient ischaemic attack (TIA), and subsequent event rates after a first recurrent IS. Adults with a first hospitalisation for NCIS or TIA between 1 January 2015 and 29 October 2022 were identified in a Japanese nationwide hospital database (N=18 719). NCIS was identified based on diagnostic codes. Clinical events were assessed after discharge of the initial and the first recurrent IS hospitalisations. Rates (per 1000 person-years (95% CIs)) of IS, death, haemorrhagic stroke, myocardial infarction or unstable angina, major bleeding, and newly diagnosed atrial fibrillation were 103.5 (100.0 to 107.0), 45.9 (43.8 to 48.1), 10.6 (9.6 to 11.7), 21.7 (20.2 to 23.2), 60.0 (57.4 to 62.5) and 22.9 (21.3 to 24.4), respectively. In the subcohort with a first recurrent IS (N=3081), rates of these events were 199.9 (186.6 to 213.1), 53.3 (46.5 to 60.2), 15.6 (11.9 to 19.4), 39.6 (33.5 to 45.6), 96.5 (87.1 to 105.9) and 52.7 (45.7 to 59.8), respectively, following the recurrent IS. Following the initial hospitalisation, antiplatelet therapy was used in 71.8% of people. However, only 54.2% of people were prescribed any antithrombotic therapy in the 90 days prior to the first recurrent IS, which increased to 77.0% after the event. The rate of recurrent IS was high in people with NCIS and more effective, tolerable prevention strategies are needed. The high rate of clinical events following a first recurrent IS may underscore the importance of preventing IS recurrence in people with NCIS.
Dedicated breast positron emission tomography (dbPET) was developed to detect breast cancers smaller than those detectable using whole-body PET (wbPET). Although several studies have explored the use of dbPET, clear criteria for identifying which patients would benefit most from this modality are lacking. Our objective was to determine which patient groups would benefit most from dbPET and how it should be utilized. We conducted a multicenter, prospective exploratory study to investigate how the dbPET maximum standardized uptake values (SUVmax) correlate with patients' clinical characteristics, other imaging modalities, and pathological findings of the lesions. In total, 219 patients with breast cancer (median age [range], 58.0 [30-83] years) were included in this study. The enrolled patients were divided into three groups (primary care, neoadjuvant therapy, postoperative follow-up patients). In this research, we examined the primary care group (n = 92). To investigate which patient groups benefit from dbPET, we examined which factors influence and correlate with dbPET SUVmax. Depending on the items being compared, correlation analysis, Wilcoxon signed rank test was used to examine the following items. Which factors (physical factors, pathological characteristics, etc.) correlate with dbPET SUVmax, differences between dbPET and other imaging examination (detection rate, etc.), and whether dbPET SUVmax L/H ratio (Lesion-to-Healthy (normal) site dbPET SUVmax ratio) incorporating dbPET SUVmax from healthy (normal) mammary gland tissue are necessary for evaluating dbPET SUVmax in lesion areas. dbPET SUVmax in healthy(normal) mammary gland tissue were strongly associated with background mammary density observed on mammography (MMG) examination (positive correlation, p<0.05). Ki-67 showed the strongest positive correlation with both the lesion-site dbPET SUVmax (r=0.56, R2=0.31, p<0.05) and the dbPET SUVmax L/H ratio (lesion-to-healthy (normal) -site ratio) (r=0.47, R2=0.22, p<0.05). Additionally, the tissue grade, MMG and ultrasonography categories were positively correlated with dbPET SUVmax. Regarding the lesion detection rate, dbPET identified 100% of the lesions, including benign findings. The dbPET SUVmax L/H ratio showed a trend nearly identical to that of the dbPET SUVmax. dbPET demonstrated higher detection capabilities than other imaging tests and showed a strong correlation with tissue malignancy. Therefore, they were suggested to be potentially useful for distinguishing benign findings from malignant lesions that are difficult to differentiate using other imaging tests. The dbPET SUVmax of healthy mammary gland tissue were presumed to correlate with the amount of mammary gland tissue within the breast. However, no significant differences were observed in the correlations between the dbPET values and the L/H ratio and the individual parameters. In this study, it remained unclear whether the dbPET values of normal breast tissue should be taken into account when evaluating dbPET values.
Linguistic abnormalities in schizophrenia (SCZ) span morphological, syntactic, semantic, and discourse levels. Converging cross-linguistic evidence suggests that SCZ may involve semantic narrowing alongside reduced syntactic differentiation, yet how these changes co-occur across linguistic domains and whether they represent core, task-general disturbances remains unclear. We applied a multilevel NLP framework to a large Japanese dataset to identify structurally related linguistic markers of SCZ across elicitation contexts. Speech from 104 patients with SCZ and 101 healthy controls was collected through semi-structured interviews. Transcripts from free conversation, storytelling, and picture description were analyzed using GiNZA, Word2Vec, TF-IDF, and SentenceBERT to extract 76 morphosyntactic, semantic, and discourse features. Factor analysis identified representative features independent of diagnosis, which were tested using generalized estimating equations and validated with bootstrap and permutation procedures. Cross-task stability was examined to determine core linguistic markers. In free conversation, reduced Case-particle (Kakujoshi) and Adverb use and increased Mean Pairwise Word Similarity were strongly associated with SCZ (AUC = 0.87, 95% CI: 0.74-0.97). Adverbial, case-particle, and semantic-network measures functioned as cross-task markers. SCZ involves multidimensional language disturbances characterized by a tripartite linguistic phenotype of diminished morphosyntactic explicitness, semantic narrowing, and reduced modification-based contextual modulation in spontaneous discourse. Extending cross-linguistic evidence, our results indicate that lexical-semantic contraction co-occurs with reduced overt marking of argument relations in Japanese, alongside weakened adverbial elaboration and framing - suggesting convergent, largely task-general dimensions of SCZ language pathology, most evident in free conversation.
Standard gastrectomy with lymph node dissection up to D1+ achieves good oncologic control for early gastric cancer not amenable to endoscopic submucosal dissection, yet it frequently leads to post-gastrectomy syndromes and long-term nutritional impairment. Local resection of the stomach reduces post-gastrectomy syndrome; however, the extent of lymph node dissection should be limited beyond D1+ in such cases. This review evaluates the safety of local resection for early gastric cancer reported in East Asia. We reviewed current concepts and clinical evidence regarding (i) the limitations of preoperative nodal staging, (ii) sentinel node biopsy and function-preserving gastrectomy, and (iii) functional outcomes and procedure-specific complications following local resection, with a focus on delayed gastric emptying. Conventional imaging and biomarkers are inadequate for reliable preoperative identification of node-negative disease. Conversely, sentinel node biopsies demonstrate high intraoperative diagnostic accuracy. Large prospective studies have revealed that, when indications are strictly adhered to, sentinel node biopsy-guided function-preserving gastrectomy can yield survival outcomes comparable to those of standard gastrectomy. The indications for local resection include solitary submucosal tumors below 4 cm in size, diagnosed as node-negative by sentinel node biopsy. Although the available quality-of-life data are generally favorable, there is risk of delayed gastric emptying in local resection with limited lymph node dissection in cases of early gastric cancer. Postoperative gastric deformity following closure was identified as the primary cause. Local resection for submucosal gastric cancer guided by sentinel node biopsy may be oncologically acceptable and function-preserving; however, the prevention of gastric deformity is crucial for its safe implementation.
Pulmonary vein stenosis after repair of total anomalous pulmonary venous connection (TAPVC) is a life-threatening complication that frequently recurs, particularly in patients with asplenia. Although intrinsic mechanisms such as ostial narrowing and progressive neointimal proliferation are well recognized, extrinsic mechanical factors are less commonly emphasized in congenital heart disease. We report a case of recurrent pulmonary vein stenosis in a patient with asplenia in whom intrinsic susceptibility and possible posterior extrinsic compression may have acted synergistically. Serial computed tomography demonstrated persistent proximity between the left pulmonary vein and indwelling enteral feeding tubes. Sustained improvement was achieved after surgical relocation of the left pulmonary vein orifice to a site remote from the tubes. This case suggests that external mechanical influences may represent an underrecognized and potentially modifiable contributor to postoperative pulmonary vein stenosis in high-risk pediatric patients.
Acinar-to-ductal metaplasia (ADM)-a process involving the dedifferentiation or transdifferentiation of pancreatic acinar cells-is recognized as an initial event in pancreatic tumorigenesis. Studies in mouse models have revealed that tuft cells, which are chemosensory epithelial cells, appear in ADM following tissue injury, and tuft cell-produced prostaglandin (PG) D2 may suppress inflammation and tumorigenesis. However, the presence and role of tuft cells in the human pancreas remain unclear. Therefore, in this study, we investigated the presence of tuft cells and PGD2 production in human ADM. We analyzed ADM lesions from consecutive patients undergoing surgical resection for pancreatic tumors using dual immunohistochemical staining for POU domain class 2 transcription factor 3 (POU2F3) and hematopoietic PGD synthase (H-PGDS). All 29 patients (13 men and 16 women) with diagnoses including pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasms exhibited ADM in regions of obstructive pancreatitis. Immunohistochemical analysis showed that 67.3% of ADM lesions contained POU2F3- and/or H-PGDS-positive cells. Among these, 85.5% of POU2F3-positive cells co-expressed H-PGDS, and 76.2% of H-PGDS-positive cells were POU2F3-positive. These findings indicate that tuft cells present in human ADM produce PGD2, suggesting a role in tissue repair. Tuft cells may represent a potential therapeutic target in pancreatitis, warranting further investigation into their functional role in ADM.
Non-canonical disulfide bonds are a hallmark of the VHH domain of heavy-chain antibodies, with predominant bonds between CDRs 1 and 3 and between framework FR2 and CDR3. The former interloop disulfide bond is advantageous for stability and antigen-binding affinity, albeit not indispensable. Importantly, mutations in the cysteine of the interloop disulfide bond of CDRs 1 and 3 can sometimes preserve antigen-binding activity. In contrast, the functional role of the interloop disulfide bond between FR2 and CDR3 remains largely understudied. In this study, we investigated the replacement of the disulfide bond between FR2 and CDR3 with cysteine mutations in aliphatic amino acids (alanine, valine, and isoleucine). These results indicate that this interloop disulfide bond contributes to the structural stabilization of VHH but is not required for antigen binding, consistent with the findings for the disulfide bond between CDRs 1 and 3. Furthermore, the disulfide bond between FR2 and CDR3 was not critical for maintaining reversibility following heat-induced unfolding. Given the prevalence of FR2-CDR3 interloop disulfide bonds in VHHs from llamas and alpacas, these findings provide valuable insights into VHH engineering and applications.
Electrospun hydrogel-forming nanofibrous mats are attractive for wound-interface and soft-tissue applications, yet mechanical fragility and poor handling often limit translation. We report an aqueous, mildly acidic coaxial electrospinning strategy to fabricate a core-shell mat with a ductile poly(ethylene oxide) (PEO) core and an acetoacetyl-functionalized poly(vinyl alcohol) (PVA) sheath crosslinked with sodium glyoxylate. The acetoacetyl/aldehyde reaction is proposed to generate stable ring-type covalent bridges in the PVA network. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirm fibers with clear core-shell architecture, while Fourier transform IR and X-ray diffraction (XRD) support formation of a stabilized hydrogel-forming PVA sheath and strong interpolymer interactions. The coaxial mat exhibits an ultimate tensile strength (UTS)/Young's modulus of 12.65/35.5 MPa compared with 7.63/133.0 MPa for crosslinked PVA and 7.64/17.8 MPa for neat PVA, respectively. Thus, the composite combines higher tensile strength than both PVA controls with intermediate stiffness-substantially softer than crosslinked PVA yet stiffer than neat PVA. Its elongation at break and toughness (53% strain, 5.2 MJ m-3) are lower than in neat PVA but comparable to crosslinked PVA, reflecting a strength-ductility trade-off. The mat retains hydrogel integrity after water exposure (swelling ratio ~ 5; gel content ~ 59%), and nitrogen sorption reveals mesoporosity with Brunauer-Emmett-Teller (BET) surface area of ~ 8 m2 g-1 and average pore diameter of ~ 8 nm. Thermogravimetric analysis shows a broadened intermediate degradation region for the coaxial mat. Overall, integrating a hydrophilic PEO core within a crosslinked PVA sheath enhances the dry state tensile strength of electrospun hydrogel-forming mat while preserving hydration and mesoporosity upon wetting, supporting further optimization for wound dressings.
Oral complications are common in palliative care and may directly impair patients' eating habits, comfort, and quality of life. Despite these impacts, dental integration remains suboptimal into supportive oncology and non-cancer palliative care models in many settings. This review synthesized current evidence and proposed a practical framework for proactive preventive dental care. A structured narrative review was conducted via the PubMed and Ichushi-Web electronic databases to identify studies indexed between 2000 and 2026. The literature addressing oral symptoms, mastication, nutrition, denture management, and interdisciplinary care in serious illnesses was included. Oral dysfunctions, including xerostomia, mucosal and dental pain, oral infections, and denture instability, are frequently reported in palliative populations and contribute to reduced dietary intake and diminished quality of life. Emerging evidence suggests that maintaining masticatory function may support nutritional stability, treatment tolerance, and patient-reported quality of life. On the basis of the synthesized literature, we propose a proactive preventive dental care (PPDC) framework that emphasizes routine oral assessment, pain management, moisturization, hygiene maintenance, early functional restoration, and interdisciplinary collaboration with nutrition and palliative teams. Integrating anticipatory dental strategies into supportive and palliative care may help preserve eating-related quality of life across both cancer and non-cancer illness trajectories. Prospective studies are needed to evaluate the clinical impact of the implementation of proactive dental care strategies in multidisciplinary supportive care.
Despite its uncommon occurrence, pulmonary metastasis from head and neck cancer has significant prognostic implications. Although pulmonary metastasectomy is a potential treatment option for select patients, its impact on patient survival remains controversial. This study aimed to describe our institutional experience with pulmonary metastasectomy for head and neck cancer and to contextualize the findings within previously published surgical series. We conducted a retrospective cohort study involving 15 patients with head and neck cancer who underwent pulmonary metastasectomy at our institution. Clinicopathological characteristics, disease-free interval, tumor size, surgical procedures, and postoperative outcomes were descriptively analyzed. The median overall survival time after pulmonary metastasectomy was 36 months. Complete resection was achieved in all patients. Patients with a longer disease-free interval tended to show more favorable survival outcomes, whereas tumor size did not demonstrate a clear association with prognosis in this cohort. Postoperative adjuvant therapy was administered in 60.0% of patients. Pulmonary metastasectomy may be a treatment option for carefully selected patients with head and neck cancer. A longer disease-free interval appears to be an important consideration for patient selection, consistent with previous reports, while tumor size alone may not be sufficient to predict outcomes. Given the retrospective design and small sample size, further multicenter studies are warranted to clarify the role of pulmonary metastasectomy in this setting.
Background/Objectives: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and decreased tear secretion, largely driven by chronic ocular surface inflammation. Although current therapies primarily target inflammation and tear film stabilization, their clinical efficacy is often limited by insufficient ocular surface retention. In this study, we explored a drug repositioning strategy for DED by developing a nanocrystalline formulation of troxipide (TRO), a gastric mucosal protective agent with cytoprotective properties. Methods and Results: A TRO nanosuspension (TRO-NPs) was successfully prepared by wet bead milling, yielding particles with a mean diameter of approximately 100 nm. Physicochemical characterization revealed that the crystalline structure, solubility, viscosity, pH, and osmolarity of the nanosuspension were comparable with those of the conventional TRO microsuspension (TRO-MPs). In contrast, the TRO-NPs exhibited markedly improved dispersion stability, maintaining particle suspension for at least 1 month after preparation. Repeated topical instillation of the TRO-NPs did not induce corneal toxicity or inflammation in rabbits, and resulted in significantly higher drug retention in the tear fluid than that observed for the TRO-MPs. Furthermore, in an N-acetylcysteine-induced rabbit dry eye model, repetitive instillation of the TRO-NPs significantly increased tear volume and mucin levels, leading to improved tear film stability. Conclusions: These findings demonstrate that nanosuspension-based formulations can enhance ocular surface retention and therapeutic efficacy of TRO. TRO-NPs therefore represent a promising nanomedicine-based repositioned therapy for the treatment of DED.
A highly sensitive analytical method for the detection of succinylcholine (SUX) and its metabolite (succinylmonocholine, SMC) in hair was established using liquid chromatography-tandem mass spectrometry with ion-pair solid-phase extraction (IP-SPE), and was applied in a murder case. SUX and SMC were detected using this method, for the first time, in hair collected from a victim 27 days after SUX injection. To investigate the distributions of SUX and SMC along hair, 2-mm sectional quantitative analysis was performed on the 0–2 cm segment, the hair region which was positive for the analytes. SUX and SMC were detected in the ranges of 4–14 mm and 6–14 mm from the root end, respectively, both with the highest concentrations in the 8–10 mm segment, which would be roughly consistent with the SUX injection to the victim 27 days earlier. The detected concentrations of SUX and SMC in the 0–2 cm segment were 1.0 pg/hair strand (8.3 pg/mg) and 0.18 pg/hair strand (1.5 pg/mg), respectively. These data demonstrate the present method has sufficient LODs to detect SUX and SMC incorporated in hair, and hair testing could be useful to prove SUX injections in the forensic fields.
Conventional assessments of lymphatic invasion in the primary tumor may fail to identify lymph node metastasis (LNM) in breast cancer. We evaluated periarterial or perivenous invasion (periA/V), using Elastica-van Gieson (EVG)-stained sections, as a histological marker associated with LNM in invasive breast carcinoma of no special type (IBC-NST), focusing on the impact of invasive tumor size. We retrospectively analyzed 213 IBC-NST cases. PeriA/V was defined as tumor nests in direct contact with perivascular elastic fibers on EVG-stained sections. Diagnostic performance was compared with that of conventional LI markers (hematoxylin and eosin and D2-40), with stratified analyses by pathological T category (pT1 vs. pT2-4) and pT1 subcategories (pT1a, pT1b, and pT1c). LNM was observed in 87 cases (40.8%). Overall, periA/V demonstrated high sensitivity (97.7%) and negative predictive value (NPV; 93.5%). In pT1 tumors (n = 130), periA/V achieved 100% sensitivity and 100% NPV (27/27), and was consistently present in all node-positive pT1b-c tumors. In multivariate analyses, periA/V remained independently associated with LNM in the pT1 group (odds ratio [OR]: 16.08, p = 0.003) and pT1c subgroup (OR: 14.7, p = 0.010). In pT2-4 tumors, periA/V became frequent regardless of nodal status, indicating reduced discriminatory value. In this exploratory single-center cohort, EVG-based periA/V demonstrated high sensitivity for LNM in pT1 IBC-NSTs, with periA/V negativity consistently observed among node-negative cases. These preliminary findings suggest that periA/V may potentially contribute to LNM risk assessment in early-stage breast cancer.
Structural analysis of nucleic acids lags behind that of proteins, partly because most fundamental structural analysis techniques have been primarily developed for proteins. The molecular replacement (MR) method, commonly used for phase determination in protein crystallography, encounters unique challenges when applied to nucleic acids. Nucleic acids can have different three-dimensional structures even with the same sequence, which often renders database entries or predicted models unsuitable as search models for MR. To overcome the limitation, we developed a novel strategy termed 4MRNA, which stands for Massive Multi-type Model Molecular Replacement for Nucleic Acids. This method introduces a new principle for MR, which is the systematic creation of diverse search models through parameter adjustment. By identifying the parameters that critically influence MR and generating models based on their statistical analysis, 4MRNA can provide search models that closely approximate target structures and thereby improve the success rate of MR. Its effectiveness was validated across comprehensive test cases including canonical duplexes, duplexes with bulges and internal loops, the more complex structure of transfer RNA, and a previously unreported DNA structure. 4MRNA is anticipated to become an indispensable tool for nucleic acid structure determination, profoundly advancing fundamental research and extending its impact to wide-ranging applications including structure-based drug design and nucleic acid nanotechnology.
Focused beam reflectance measurement (FBRM) has been used for investigating tablet dissolution behavior. However, few studies have used FBRM to analyze sustained-release formulations. In this study, we prepared tablets containing hydroxypropyl methylcellulose (HPMC), a widely used sustained-release excipient, and evaluated dissolution behavior using both conventional dissolution testing and FBRM. To assess the effect of drug solubility on FBRM parameters, we also compared acetaminophen (readily soluble in water) with ethenzamide (poorly soluble in water). Conventional dissolution testing revealed a difference of approximately 360 min among the different HPMC grades in the time required to reach 60% drug release, while FBRM detected an approximate threefold difference in the final particle counts. These findings suggest that FBRM is a useful analytical tool for elucidating the dissolution behavior of sustained-release formulations.
The hyperphosphorylation of α-synuclein (α-Syn) at serine 129 is associated with in its aggregation, culminating in the formation of Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs. Plasma homocysteine (Hcy) levels are typically high in PD, particularly in those treated with Levodopa. Therefore, we aimed to investigate the effects of Hcy on phosphorylation and aggregation of α-Syn. The human neuroblastoma cell line 3D5 expressing wild-type α-Syn under the control of a tetracycline-off system was treated with Hcy, and aggregation and phosphorylation of α-Syn were examined. Hcy was cytotoxic to 3D5 cells, and Hcy induced cell shrinkage at a concentration >100 ‍μM. Treatment with Hcy upregulated the levels of α-Syn, increased its phosphorylation at serine 129, and increased casein kinase 2A. Moreover, Hcy treatment significantly increased the level of aggregated form of α-Syn, including oligomers in 3D5 cells. However, folate significantly reversed the Hcy-mediated increase in the levels of total α-Syn and its phosphorylation. In conclusion, Hcy enhances the total α-Syn level, and phosphorylated and oligomeric α-Syn formation, thereby promoting LBs formation.
Area under the concentration-time curve (AUC)-guided dosing for vancomycin requires the measurement of both peak and trough concentrations. Recently, a novel population pharmacokinetic model (Bayesian-based, free-web application PAT version 4.0) was developed. The aim of the present study was to verify whether this optimized pharmacokinetic model improved the predictive accuracy of AUC calculated using trough-only data compared to data obtained using trough and peak sampling on Day 2. We conducted a single-center, cohort study to evaluate the agreement of AUC calculated using trough-only data compared to peak-trough sampling on Day 2, and to compare results obtained with the Yasuhara (previous) and Oda (updated) pharmacokinetic models. The proportion of trough/peak-trough AUC24-48 ratios within a 5% difference was significantly higher with the Oda model than with the Yasuhara model (75 vs. 58.3%, p = 0.034). Furthermore, multivariate logistic regression analysis showed that implementation of the Oda model was a significant factor associated with deviation of trough/peak-trough AUC24-48 within 5% (odds ratio 2.36, 95% confidence interval, 1.05-5.05, p = 0.027). The updated model offers enhanced predictive performance for AUC24-48 estimation using trough-only data. Further development of strategies to improve the predictive accuracy of AUC24-48 using trough-only data is warranted.
Boron neutron capture therapy (BNCT) is a tumor-selective radiation modality that delivers high-linear energy transfer alpha and Lithium-7 particles to boron-containing cells following neutron irradiation. While both preclinical and clinical investigations of BNCT for intracranial tumors have primarily focused on solitary lesions, brain metastases frequently present as multifocal disease in clinical practice. The therapeutic efficacy of BNCT in this setting remains insufficiently explored. We evaluated the therapeutic efficacy of BNCT in rat models of solitary and multiple brain metastases established using a syngeneic breast cancer cell line. Boronophenylalanine was administered intravenously prior to neutron irradiation. Survival outcomes were compared among untreated controls, neutron irradiation alone, and BNCT groups. Boron biodistribution was analyzed to determine optimal irradiation timing, and treatment safety was assessed by longitudinal monitoring of body weight. BNCT significantly prolonged post-irradiation survival compared with neutron irradiation alone and untreated controls in both solitary and multiple tumor models. Notably, a substantial survival benefit was maintained even in the multiple brain metastasis model, despite the presence of spatially distributed intracranial tumor burden. Biodistribution analysis demonstrated preferential boron accumulation in tumor tissue relative to normal brain. Body weight monitoring indicated no significant treatment-related toxicity. BNCT demonstrated therapeutic efficacy and feasibility in a preclinical model of multiple brain metastases, providing a survival benefit without excessive toxicity. These findings support further investigation of BNCT as a potential treatment strategy for multifocal intracranial disease.