Okayama Medical Center

Temperature sensing shapes behavior and cellular functions, yet the molecular basis of thermosensitivity in non-neuronal cells remains poorly defined. Microglia are resident immune cells of the central nervous system that help maintain brain homeostasis via immune surveillance and injury responses. We previously showed that microglial motility is temperature dependent and is largely mediated by the thermosensitive ion channel transient receptor potential vanilloid 4 (TRPV4), a thermosensitive ion channel. However, the contribution of transient receptor potential melastatin 4 (TRPM4) is unclear because suitable Trpm4 mutant mice were not available in our earlier work. Here, we generated functional Trpm4-knockout mice (TRPM4KO) using CRISPR/Cas9 genome editing based on a published strategy. Time-lapse imaging of primary microglia across a range of temperatures revealed that Trpm4 deficiency did not alter temperature-dependent motility in vitro. These results indicate that TRPM4 is dispensable for temperature-dependent microglial motility.

Severe hypoglycemia (SH) is a major complication in adults with type 1 diabetes mellitus (T1DM). The multifactorial etiology of T1DM highlights the need for predictive tools that integrate clinical, behavioral, and technological factors. This study aimed to develop and evaluate machine learning (ML) models for predicting SH by incorporating hypoglycemia problem-solving ability, diabetes technology, and continuous glucose monitoring (CGM) indices. We analyzed data from 247 adults with T1DM (mean age 50.4 ± 13.7 years; 38.1% male; glycosylated hemoglobin 7.7 ± 0.9%) from the FGM-Japan study. A total of 22,517 feature-model combinations were evaluated across 11 ML algorithms, including logistic regression, L1-regularized regression, random forest, LightGBM, XGBoost, SVM, Naïve Bayes, SGD, neural networks, and k-nearest neighbors. Eleven candidate predictors included impaired awareness of hypoglycemia (IAH), diabetic peripheral neuropathy (DPN), CSII, rtCGM, and seven domains of hypoglycemia problem-solving ability. The model performance was assessed with fivefold cross-validation using the receiver operating characteristic-area under the curve (ROC-AUC), accuracy, precision, recall, and F1 score. Class imbalance was addressed using SMOTE. The mean ROC-AUC across models was 0.64 (range: 0.151-0.916). The average accuracy was 0.90, but the precision and recall were consistently low, with a mean recall of 0.08. The high-performing models (ROC-AUC > 0.90) were primarily Random Forest and LightGBM, which frequently incorporated domains such as problem perception, identifying problem attributes, seeking preventive strategies, evaluating strategies, and immediate management. factors. Tree-based models significantly outperformed logistic regression, Naïve Bayes, SVM, and SGD (adjusted p < 0.001), whereas the differences among the tree-based algorithms were not clinically meaningful. Tree-based ML models demonstrated superior discriminative ability for predicting SH in patients with T1DM. Hypoglycemia problem-solving ability was the strongest predictor, underscoring the importance of integrating behavioral self-management skills with clinical and technological factors. University hospital Medical Information Network (UMIN) Center: UMIN000039475), Approval date 13 February 2020.

Dental prostheses account for a large proportion of airway foreign bodies. When complicated by obstructive pneumonia, airway edema and secretions may impair visibility and manoeuvrability, making retrieval more difficult. We report two cases of airway foreign bodies caused by dental prostheses complicated by obstructive pneumonia. Case 1 involved a 78-year-old man with a crown impacted in the left lower lobe bronchus, which was retrieved with flexible bronchoscopy under intravenous anaesthesia despite difficulty. Case 2 involved a 68-year-old man with a metal core post and crown impacted in the right basal trunk bronchus with granulation tissue, and retrieved with rigid bronchoscopy under general anaesthesia. In Case 1, flexible bronchoscopic retrieval was difficult owing to coughing and secretions. Therefore, in Case 2, we selected rigid bronchoscopy and administered antibiotic therapy before retrieval. These cases underscore the importance of selecting retrieval devices based on the foreign body's characteristics and the clinical situation.

ABSTRACTIn the winter of 2025, a novel balloon‐less convex‐probe endobronchial ultrasound bronchoscope (BLCP‐EBUS) (Fujifilm EB‐710US) was introduced in Japan. It features a balloon‐less design, flexible distal tip, improved angulation, and reduced outer diameter, though clinical experience remains limited. Here we report our initial experience using the EB‐710US for EBUS‐guided transbronchial needle aspiration (EBUS‐TBNA) and endoscopic ultrasound‐guided fine‐needle aspiration via the bronchus (EUS‐B‐FNA). An 86‐year‐old man with mediastinal lymphadenopathy underwent EBUS‐TBNA of a left lower paratracheal lymph node (station #4L). Adequate lesion contact and stable needle aspiration were achieved without a balloon, enabling successful tissue collection and adenocarcinoma diagnosis. A 73‐year‐old man required a re‐biopsy for a multiplex driver mutation test, and EUS‐B‐FNA of lymph node #8 was performed using a novel bronchoscope. Both procedures were safely completed under conscious sedation, with positive rapid on‐site cytology evaluation and sufficient tissue for adenocarcinoma diagnosis. The novel BLCP‐EBUS bronchoscope (EB‐710US) demonstrated favourable manoeuvrability and adequate lesion contact for both EBUS‐TBNA and EUS‐B‐FNA. The novel bronchoscope may enhance procedural safety, patient comfort, and diagnostic yield.

ABSTRACTA 49‐year‐old man with severe airway stenosis and SVC syndrome underwent urgent Y‐stent placement before diagnosis. Subsequent EUS‐B‐FNA enabled adenocarcinoma diagnosis. This case highlights that transbronchial biopsy in marked stenosis risks fatal obstruction; thus, transesophageal biopsy should be prioritised to ensure safe diagnosis and genomic testing.

Some ALK-positive lung cancers show early resistance to alectinib. This study found brain metastases and elevated NLR associated with early resistance. Spatial transcriptomics and functional analysis suggested involvement of ANXA1. These results reveal clinical and molecular biomarkers that may guide treatment strategies for early resistance to alectinib.

Endotracheal and endobronchial metastases from peripheral lung adenocarcinoma are rare, and optimal clinical management remains unclear. We herein report a 60-year-old woman with epidermal growth factor receptor (EGFR) exon 19 deletion-positive early-stage lung adenocarcinoma who underwent surgical resection followed by osimertinib treatment for recurrence. She later developed oligoprogressive disease with airway metastases. Bronchoscopic tumor removal was performed, and next-generation sequencing of the resected specimen revealed an acquired EGFR C797S mutation, along with exon 19 deletion. Gefitinib treatment was initiated, which led to a partial response. This case underscores the utility of repeated molecular profiling and local intervention in managing acquired resistance in EGFR-mutant non-small-cell lung cancer.

<bold>Background:</bold> Upfront combination therapy based on risk stratification using the 3-strata model recommended in the guidelines is associated with an improvement in survival in patients with classical pulmonary arterial hypertension (PAH). Meanwhile, combination therapy for PAH patients with comorbidities is not aggressively recommended because of intolerance for vasodilators, and the long-term prognosis by risk stratification remains unclear. <bold>Methods:</bold> This study included 114 patients with I/HPAH and CTD-PH, classified as classical PAH and PAH with comorbidities who had at least one comorbidity. Long-term survival was investigated by the 3-strata model. <bold>Results:</bold> Classical PAH and PAH with comorbidities comprised 42 and 72 patients. The percentage of upfront combination therapy, including parenteral prostaglandin I2, was higher for classical PAH than PAH with comorbidities (83% vs. 9%, p<0.001). Although the mean PAP at baseline was higher for classical PAH than for PAH with comorbidities (49±16 vs. 39±12mmHg, p<0.001), the 10-year survival rate for classical PAH was significantly higher than for PAH with comorbidities (96% vs 46%, p<0.001). In the 3-strata model, while 10-year survival rates for classical PAH were higher in all risk groups (low 100%, intermediate 96%, and high 100%, p=0.882), those for PAH with comorbidities depended on risk stratification (low 100%, intermediate 46%, and high 0%, p=0.005). <bold>Conclusions:</bold> The 10-year survival rate for PAH with comorbidities was significantly lower than that of classical PAH. Unfavorable outcomes for PAH with comorbidities might derived from the lower proportion of patients who can tolerate upfront combination therapy.