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Dental pulp stem cells (DPSCs) demonstrate high proliferative and multilineage differentiation potential. As previously reported, the helioxanthin derivative 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH) has been demonstrated to induce the osteogenic differentiation of DPSCs. However, the mechanism of osteogenesis induced by TH in DPSCs remains unknown. The objective of this study was to identify functional extracellular vesicle (EV) microRNAs (miRNAs), and the principal genes involved in the TH-induced osteogenesis of DPSCs. DPSCs were derived from dental pulp extracted from the third molars of three healthy subjects, and were cultured with or without TH. miRNAs were extracted from DPSC-derived EVs. The gene expression patterns of mRNA and miRNA were compared using RNA-Seq and miRNA-Seq. To investigate miRNA/mRNA interacting networks, functional analyses were performed by Ingenuity Pathway Analysis. Alkaline phosphatase (ALP) staining demonstrated that treatment with TH resulted in enhanced ALP activity in DPSCs after 7 days. The expression levels of ALP and type 1 collagen alpha 1 were significantly higher in TH-induced DPSCs on day 7. RNA-Seq and miRNA-Seq analyses identified 869 differentially expressed genes (DEGs) and 18 miRNA-DEGs. Gene Ontology analysis of the mRNA-Seq results showed that TH induced several biological activities associated with signal transduction, cell adhesion, and cell differentiation. Integrated miRNA-mRNA analyses showed that these miRNAs contain the targeting information of 277 mRNAs of the DEGs. Among them, 17 target genes known to be involved in the differentiation of osteoblasts, and 24 target genes known to be involved in the differentiation of bone cells were identified. Quantitative real-time PCR showed that WNT5a expression in DPSCs was upregulated by 48 h of TH treatment. Upstream regulator analysis indicated that WNT3a, FOS, and RAC1 may be responsible for gene expression changes in DPSCs after TH treatment. EV miRNA regulatory networks might play crucial roles in TH-induced osteogenic differentiation of DPSCs. Our results presented herein offer valuable insights that will facilitate further research into the mechanism of osteogenesis of DPSCs, which is expected to lead to the clinical application of TH-induced DPSCs for bone regeneration. Furthermore, EVs derived from TH-induced DPSCs might be useful as therapeutic tools for bone defects.

Construction work and regular inspection work at nuclear power plants involve many special tasks, unlike general on-site work. In addition, the opportunity to transfer knowledge from skilled workers to unskilled workers is limited due to the inability to easily enter the plant and various security and radiation exposure issues. Therefore, in this study, we considered the application of virtual reality (VR) as a method to increase opportunities to learn anytime and anywhere and to transfer knowledge more effectively. In addition, as an interactive learning method to improve comprehension, we devised a system that uses hand tracking and eye tracking to allow participants to experience movements and postures that are closer to the real work in a virtual space. For hand-based work, three actions, “pinch”, “grab”, and “hold”, were reproduced depending on the sizes of the parts and tools, and visual confirmation work was reproduced by the movement of the gaze point of the eyes, faithfully reproducing the special actions of the inspection work. We confirmed that a hybrid learning process that appropriately combines the developed active learning method, using experiential VR, with conventional passive learning methods, using paper and video, can improve the comprehension and retention of special work at nuclear power plants.

Abstract Background Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p

Abstract The number of patients with atrial fibrillation is increasing, and frailty prevalence increases with age, posing challenges for physicians in prescribing anticoagulants to such patients because of possible harm. The effects of frailty on anticoagulant therapy in older Japanese patients with nonvalvular atrial fibrillation (NVAF) are unclear. Herein, we prescribed rivaroxaban to Japanese patients with NVAF and monitored for a mean of 2.0 years. The primary endpoint was stroke or systemic embolism. The secondary endpoints were all-cause or cardiovascular death, composite endpoint, and major or non-major bleeding. Frailty was assessed using the Japanese long-term care insurance system. A multiple imputation technique was used for missing data. The propensity score (PS) was obtained to estimate the treatment effect of frailty and was used to create two PS-matched groups. Overall, 5717 older patients had NVAF (mean age: 73.9 years), 485 (8.5%) were classified as frail. After PS matching, background characteristics were well-balanced between the groups. Rivaroxaban dosages were 10 and 15 mg/day for approximately 80% and the remaining patients, respectively. Frailty was not associated with the primary endpoint or secondary endpoints. In conclusion, frailty does not affect the effectiveness or safety of rivaroxaban anticoagulant therapy in older Japanese patients with NVAF. Trial registration: UMIN000019135, NCT02633982.

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 acyl ester linkage in phospholipid, producing lysophospholipid and fatty acid in the presence of Ca2+. The hydrolysis mediated by PLA2 has attracted much interest in various fields, such as pharmacy and biotechnology. It is recognized that PLA2 cannot hydrolyze phospholipid monolayers at high surface coverage. However, the origin of different PLA2 activities is not fully understood yet. The present study investigated the interaction between DPPC (16:0 PC) monolayer and PLA2 using heterodyne-detected sum frequency generation spectroscopy, which is interface-specific spectroscopy and highly sensitive to molecular symmetry based on a second-order nonlinear optical process. It was revealed that PLA2 adsorbs to the DPPC monolayer on the aqueous solution surface only when the surface coverage is low. The adsorption at the low surface coverage significantly changes the interfacial structures of PLA2 and the hydration, which are stabilized by the presence of Ca2+. Therefore, the restriction of the hydrolysis of phospholipid monolayers at high surface coverage can be rationalized by the inhabitation of the PLA2 adsorption. The present study deepens our molecular-level understanding of the hydrolysis of phospholipids by PLA2. [ABSTRACT FROM AUTHOR]

Purpose This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. Methods We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II or III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. Results The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P

Objective: Evaluate the efficacy of a new orthotic-made super-elastic alloy brace to correct hallux valgus (HV) deformity. Methods: Five female patients diagnosed with HV deformity wore the newly developed orthotic daily for six weeks. The orthotic was developed using a super-elastic alloy brace to correct great toe lateral deviation, first metatarsal medial deviation, and fixation belts. The correction was evaluated by measuring the load at which the big toe begins to move and the distance moved by 15 gf force when pulled from the side. Results: The orthotic was worn by all patients without causing any sleep disruptions. In the initial state, a strong force was required to move the big toe, but after two weeks, it was significantly improved to be mobile in all patients. Conclusion: The developed HV orthotic has a high wearability without causing pain or discomfort. Long-term use can provide a consistent and continuous correction force to the big toe, resulting in the successful release of the big toe metatarsophalangeal joint contracture within two weeks. Level of Evidence: Level 4.

IntroductionA knee-ankle-foot orthosis (KAFO) prevents knee buckling during walking and enables gait training for acute hemiplegic stroke patients with severe gait disturbances. Although the goal of gait training with a KAFO is to improve gait ability, that is, to acquire walking with an ankle-foot orthosis (AFO), it is not clear how gait training with a KAFO contributes to improving gait ability. Therefore, this study aimed to investigate the relationship between muscle activities during walking with a KAFO and the improvement of gait ability in hemiplegic stroke patients with severe gait disturbance.MethodsA prospective cohort study was conducted. Fifty acute hemiplegic stroke patients who could not walk with an AFO participated. Muscle activities of the paretic rectus femoris, biceps femoris, tibialis anterior, and soleus were assessed with surface electromyogram during walking with a KAFO. Electromyograms were assessed at the beginning of gait training and at the time the Ambulation Independence Measure score improved by 3 or higher, or discharge.ResultsEven in patients with complete hemiplegia, paretic rectus femoris, biceps femoris, and soleus showed periodic muscle activity during walking with a KAFO. Twenty-three patients improved to an Ambulation Independence Measure score of 3 or higher and were able to walk with an AFO (good recovery group). At the beginning of gait training, paretic rectus femoris muscle activity during the first double-limb support phase was significantly higher in the good recovery group than in the poor recovery group. The rectus femoris muscle activity significantly increased from before to after acute rehabilitation, which consisted mainly of gait training with a KAFO.DiscussionFor acute hemiplegic stroke patients with severe disturbance, the induction and enhancement of paretic quadriceps muscle activity during walking with a KAFO play an important role in acquiring walking with an AFO.

Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug. In this post hoc analysis, we analyzed a total of 643 T2D patients (GLP1Ra-preceding group, n = 331; SGLT2i-preceding group, n = 312) and investigated the differences in annual eGFR decline. Multiple imputation and propensity score matching were performed to compare the annual eGFR decline. The reduction in annual eGFR decline in the SGLT2i-preceding group (pre: −3.5 ± 9.4 mL/min/1.73 m2/year, post: −0.4 ± 6.3 mL/min/1.73 m2/year, p < 0.001), was significantly smaller after the initiation of GLP1Ra, whereas the GLP1Ra-preceding group tended to slow the eGFR decline but not to a statistically significant extent (pre: −2.0 ± 10.9 mL/min/1.73 m2/year, post: −1.8 ± 5.4 mL/min/1.73 m2/year, p = 0.83) after the initiation of SGLT2i. After the addition of GLP1Ra to SGLT2i-treated patients, slower annual eGFR decline was observed. Our data raise the possibility that the renal benefits—especially annual eGFR decline—of combination therapy with SGLT2i and GLP1Ra may be affected by the preceding drug.

Current methods for fabricating microparticles offer limited control over size and shape. Here, we demonstrate a droplet microfluidic method to form polyhedral microparticles with controlled concavity. By manipulating Laplace pressure, buoyancy, and particle rheology, we generate microparticles with diverse shapes and curvatures. Additionally, we demonstrate the particles provide increased capture efficiency when used for particle-templated emulsification. Our approach enables microparticles with enhanced chemical and biological functionality.

Targeting specific cells for sequencing is important for applications in cancer, microbiology, and infectious disease. Nucleic acid cytometry (NAC) is a powerful approach for accomplishing this because it allows specific cells to be isolated based on sequence biomarkers that are otherwise impossible to detect. However, existing methods require specialized microfluidic devices, limiting adoption. Here, a modified workflow is described that uses particle-templated emulsification (PTE) and flow cytometry to conduct the essential steps of cell detection and sorting normally accomplished by microfluidics. Our microfluidic-free workflow allows facile isolation and sequencing of cells, viruses, and nucleic acids and thus provides a powerful enrichment approach for targeted sequencing applications.

Abstract Background Female sex and younger age are reported risk factors for chemotherapy‐induced nausea and vomiting (CINV) in highly emetogenic chemotherapy, but the underlying mechanism has not been elucidated. The purpose of this study was to clarify the impact of menopause on CINV. Methods This retrospective observational study analyzed data from consecutive patients who received their first cycle of perioperative anthracycline‐based chemotherapy for breast cancer between January 2018 and June 2020. The endpoints were association between CINV (vomiting, ≥Grade 2 nausea, complete response [CR] failure) and menopause as well as the association between CINV and follicle‐stimulating hormone [FSH]/estradiol [E2]. Results Data for 639 patients were analyzed. Among these patients, 109 (17.1%) received olanzapine (four antiemetic combinations) and 530 (82.9%) did not (three antiemetic combinations). Premenopausal state (amenorrhea lasting ≥12 months) was significantly associated with ≥Grade 2 nausea and CR failure in univariate analysis but not in multivariate analysis. The premenopausal FSH/E2 group (defined by serum levels; FSH

Abstract Vasoconstriction during tachyarrhythmia contributes to maintenance of arterial pressure (AP) by decreasing peripheral blood flow. This cross-sectional observational study aimed to ascertain whether the relationship between peripheral blood flow and AP recovery occurs during both paroxysmal supraventricular (PSVT, n = 19) and ventricular tachycardias (VT, n = 17). Peripheral blood flow was evaluated using forearm tissue oxygen index (TOI), and mean AP (MAP) was measured using a catheter inserted in the brachial or femoral artery during an electrophysiological study. PSVT and VT rapidly decreased MAP with a comparable heart rate (P = 0.194). MAP recovered to the baseline level at 40 s from PSVT onset, but not VT. The forearm TOI decreased during both tachyarrhythmias (P ≤ 0.029). The TOI response was correlated with MAPrecovery (i.e., MAP recovery from the initial rapid decrease) at 20–60 s from PSVT onset (r = -– 0.652 to – 0.814, P ≤ 0.0298); however, this association was not observed during VT. These findings persisted even after excluding patients who had taken vasoactive drugs. Thus, restricting peripheral blood flow was associated with MAP recovery during PSVT, but not VT. This indicates that AP recovery depends on the type of tachyarrhythmia: different cardiac output and/or vasoconstriction ability during tachyarrhythmia.

Background: New tobacco products, particularly heated tobacco products (HTPs), have been introduced across several international markets as alternatives to combustible products, such as cigarettes. However, there are limited studies on physicians’ perceptions of HTPs. This study analyzes the awareness of HTPs among physicians and assesses their concerns and attitudes toward patients using HTPs. Methods: A self-administered questionnaire was sent to a sample of 7,500 member physicians (6,000 male and 1,500 female) from the Japan Medical Association (JMA). The smoking status of physicians was categorized as never smokers, ever HTP smokers, current HTP smokers, and ever and current smokers of other products. Physicians’ awareness and attitudes toward patients using HTPs were analyzed using descriptive statistics. The correlation between the outcomes was examined using logistic regression models, whereas physicians’ concerns about HTPs were analyzed using descriptive statistics. Results: Data were obtained from 5,492 physicians (21.9% women; aged 60.4; standard deviation, 12.1 years) with a response rate of 74.6%. Overall, 76.7% of the physicians had awareness of HTP, and about half of whom asked patients about using HTPs. Physicians who took longer to discuss cessation were more likely to discourage patient use. Smoking status was associated with discouraging HTP use in patients. Physicians who had experience with HTP use were primarily concerned about the products’ long-term safety and less about product regulation. Conclusion: Japanese physicians do not have sufficient information and knowledge about HTPs. Therefore, evidence-based guidelines are required to support physicians in advising patients against HTP use.