Objective: Using finite element method (FEM) analysis of a clear aligner (CA), this study aimed to investigate the effects of varying the edentulous space on canine distal bodily movement during space closure following maxillary first premolar extraction. Methods: FEM analysis was used to simulate distal canine bodily movement following maxillary first premolar extraction using CAs. Four CA designs for edentulous spaces were compared: no-pontic, full-pontic, halfpontic, and beam. Three-dimensional models of the tooth components and CA were created. The target was set at a 0.25-mm distal canine movement. Long-term tooth movement was simulated using an iterative calculation method. Results: All the groups initially showed crown displacement, distal tipping, and distal rotation.Over time, the movement patterns differed in relation to the design. The no-pontic design exhibited the greatest displacement and tipping. The beam design exhibited the largest initial displacement but showed the lowest displacement and tipping thereafter. Full- and half-pontic designs yielded intermediate results. Significant force reduction was observed immediately after CA application, and was followed by a gradual decrease. The mean tooth-movement achievement rate was approximately 76.7%. Conclusions The edentulous space design of the CA substantially affected tooth-movement behavior. An iterative simulation is necessary to evaluate longterm tooth-movement patterns. The beam design demonstrated optimal suitability for bodily movement with minimal tipping. For optimal results, additional setup or overcorrection may be necessary.

Objective: To quantitatively analyze and compare the forces and moments generated by thermoformed polyethylene terephthalate glycol (PETG) and direct-printed TC-85 clear aligners (CAs), with various margin designs, during premolar rotation. Methods: In total, 132 CAs were fabricated and divided into four groups (n = 33 per group). Group C consisted of thermoformed PETG aligners with a 2 mm gingival margin. Group E comprised direct-printed TC-85 aligners with equi-gingival margin, whereas Group G utilized direct-printed TC-85 aligners with 2 mm gingival margins.Finally, Group T featured direct-printed TC-85 aligners with an additional 1 mm thickness at the mesial embrasure. The forces and moments were measured using a 6-axis force/moment transducer at 2°, 3°, and 4° of rotation. All measurements were conducted at 37°C to simulate intraoral conditions. Forces were measured in the buccolingual, anteroposterior, and vertical directions, while moments were measured in the mesiodistal, buccolingual, and rotational planes. Results: The PETG aligners (Group C) showed significantly increased buccal and posterior force across the rotation angles (P < 0.05), whereas the intrusive force remained consistent. In contrast, the TC-85 aligners maintained consistent forces across all rotation angles.Direct-printed aligners demonstrated significantly lower intrusive forces than PETG aligners (P < 0.001). Group T exhibited reduced unwanted forces while maintaining effective rotational moments. Furthermore, all direct-printed aligners showed more predictable force delivery patterns than thermoformed aligners. Conclusions Direct-printed TC-85 aligners demonstrated superior force consistency and reduced unwanted side effects compared with traditional PETG aligners. Although marginal design modifications did not significantly improve rotational efficiency, they effectively reduced unwanted intrusive forces.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Background: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen. Methods: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. The study is registered with ClinicalTrials.gov (NCT04485156) Results: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups. Conclusion The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background: The oxygen reserve index (ORi) noninvasively measures oxygen levels within the mild hyperoxia range. To evaluate whether a degree of increase in the ORi during preoxygenation for general anesthesia is associated with the occurrence of postoperative pulmonary complications (PPCs). Methods: We enrolled 154 patients who underwent preoperative pulmonary function tests and were scheduled for elective surgery under general anesthesia. We aimed to measure the increase in ORi during preoxygenation before general anesthesia and analyze its association with PPCs. Results: PPCs occurred in 76 (49%) participants. Multivariate logistic regression analysis revealed that the three-minute preoxygenation ORi was significantly associated with PPCs (Odds ratio [OR]: 0.02, 95% CI [0.00–0.16], P < 0.001). The areas under the curve (AUC [95% CI]) in the receiver operating characteristic curve analysis for the three-minute preoxygenation ORi for PPCs were 0.64 (0.55–0.73). After a subgroup analysis, multivariate logistic regression showed that the three-minute preoxygenation ORi was significantly associated with PPCs among patients who underwent thoracic surgery (OR: 0.01, 95% CI [0.00–0.19], P = 0.006). The AUC of the three-minute preoxygenation ORi for PPCs was 0.72 (0.57–0.86) in patients who underwent thoracic surgery. Conclusions A low ORi measured after 3 min of preoxygenation for general anesthesia was associated with an increased risk of PPCs, including those undergoing thoracic surgery. This study demonstrated the potential of ORi, measured after oxygen administration, as a tool for evaluating lung function that complements traditional lung function tests and scoring systems.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.