Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Purpose: Corneal melanoma (CM) is a rare malignancy that develops from melanocytes within the cornea, constituting a minority of all ocular tumors. In this study, we sought to investigate the clinicopathological characteristics correlated with the prognosis of CM patients. Methods: We collected patients with CM between 1983 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards regression was used for univariate analysis to value hazard ratio of malignant CM versus spindle cell melanoma and nodular melanoma subgroups. Kaplan-Meier survival analysis and log-rank test were also performed to identify additional prognostic markers and confirm the findings of the Cox hazard ratio. Results: A total of 29 eligible patients were collected in our study. Age at diagnosis, laterality, primary site, tumor size, the extent of disease, marital status, income, residential area, and treatment showed no significant prognostic factors for CM patients (p > 0.05). However, when concerned with the primary site of malignant melanoma, spindle cell melanoma and nodular melanoma were found to show significantly poorer prognosis in CM patients (both p < 0.05). Conclusions Age at diagnosis, laterality, primary site, tumor size, the extent of disease, and treatment were not significant prognostic indicators for CM patients. Spindle cell melanoma and nodular melanoma were notable for showing worse survival outcomes than malignant melanoma. Although the sample size in the SEER database was limited, our findings may provide motivation for tailoring individualized treatments for patients with CM with different primary sites.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

Objective: There is increased use of 3-dimensional (3D)-printing for manufacturing of interbody cages to create microscale surface features that promote bone formation. Those features may be vulnerable to abrasion and/or delamination during cage impaction. Our objective was to quantify loss of mass and changes in surface topography of 3D-printed titanium interbody cages due to surgical impaction. Methods: Eight surfaces of four 3D-printed titanium modular interbody fusion cages were tested. The cages were impacted into the Sawbones model with compression preload of either 200N or 400N using a guided 1-lb (0.45 kg) drop weight. Mass and surface roughness parameters of each endplate were recorded and compared for differences. Results: Significant weight loss was observed for the superior endplate group and for both 200N and 400N preloads. For pooled data comparison, significant postimpaction decreases were observed for mean roughness, root-mean-squared roughness, mean roughness depth, and total height of roughness profile. No significant differences were observed for profile skewness and kurtosis. There were significant changes in almost all roughness parameters in the anterior region of the cage postimpaction with significant changes in 2 out of 6 parameters in the middle, posterior, and central regions postimpaction. Conclusion Three-dimensional-printed titanium interbody fusion cages underwent loss of mass and alteration in surface topography during benchtop testing replicating physiologic conditions. There was an endplate- and region-specific postimpaction change in roughness parameters. The anterior surface experienced the largest change in surface parameters postimpaction. Our results have implications for future cage design and pre-approval testing of 3D-printed implants.

Objectives: Vertebral fractures are associated with disability and mortality, but most vertebral fractures are asymptomatic. The present study aimed to determine the incidence of and develop a predictive nomogram for asymptomatic vertebral fractures in Vietnamese adults. Methods: This cohort study as a part of the Vietnam Osteoporosis Study involved 168 men and 287 women aged 50 years and older without a clinically diagnosed vertebral fracture. Their spine x-rays were taken at the recruitment and subsequent 2-year visit. Vertebral fractures were ascertained using the Genant’s semiquantitative method. We employed the Bayesian Model Averaging method to search for the optimal model for predicting asymptomatic vertebral fractures. A predictive nomogram was also developed to facilitate risk prediction. Results: During a median of 2.38 years of follow-up, 13 men and 16 women developed an asymptomatic vertebral fracture, yielding the overall incidence rate of 28 fractures per 1000 person-years, or 33 fractures/1000 personyears in men and 24 fractures/1000 person-years in women, respectively. Most asymptomatic vertebral fractures were moderate, almost 1.5 times more common than mild fractures. The optimal model for predicting incident asymptomatic vertebral fractures included age, male sex and lower femoral neck T-score. The area under the receiver’s operating characteristic curve was 0.91, with 95% CI ranging from 0.86 to 0.96. Conclusions Asymptomatic vertebral fractures were relatively common among adults in Vietnam. A simple model with sex, age and femoral neck T-score is helpful for selective screening of asymptomatic vertebral fractures in Vietnamese individuals.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Background: Neutrophil elastase (NE) has been proposed as a potential biomarker for evaluating the severity and prognosis of bronchiectasis. This study aimed to compare bronchial lavage quantification of NE levels and activities with those of sputum. Methods: A cross-sectional study was conducted in which 24 Vietnamese adults with bronchiectasis were enrolled from June 2023 to August 2023. All participants underwent bronchoscopy to collect bronchial lavage fluid (BLF) from two bronchial locations: one in the region with the greatest bronchial dilatation and one in the normal bronchi or in patients with all lobes affected, the least abnormal lobe (abnormal BLF [ABLF] and normal BLF [NBLF], respectively). Spontaneously expectorated sputum was also collected. Results: Out of 24 cases, the prevalence of mild, moderate and severe bronchiectasis was 14/24 (58.4%), 5/24 (20.8%), and 5/24 (20.8%), respectively. NE concentration and activity were significantly higher in sputum and ABLF than in NBLF (p<0.001). Sputum and ABLF were highly correlated (r=0.841, p<0.001) with no significant difference in NE activity between sputum and ABLF. Higher levels of NE activity were seen in more severe bronchiectasis than in mild bronchiectasis in all samples but were only statistically significant for NE activity in sputum (r=0.418, p=0.042). Conclusion NE activity and concentration are elevated in areas of the lung most affected by bronchiectasis. Sputum is a valid surrogate of pulmonary NE levels, as they correlate strongly with ABLF and confirm in a Vietnamese population the relationship between NE activity and disease severity.

Incidental gallbladder cancer (iGBC) diagnosed post-histopathological examination of gallbladders removed assuming benign gallstone disease constitutes a significant proportion of GBC patients. Most iGBC patients present with early-stage disease. The standard care for localized (non-metastatic) iGBC includes a reoperation for complete extended (radical) cholecystectomy involving liver resection and lymphadenectomy, followed by postoperative adjuvant systemic therapy. However, a major drawback of this approach is the high recurrence rate within six months post-radical surgery, which undermines the benefits of the extensive procedure; notably, most recurrences are distant, highlighting the efficacy of systemic therapy. Similar to other gastrointestinal cancers, there appears to be a potential for neoadjuvant systemic therapy (chemotherapy) before reoperative surgery in iGBC cases. The premise that neoadjuvant systemic therapy aids in selecting diseases with more favorable biological characteristics and addresses micro-metastatic disease appears applicable to iGBC as well. This systematic review examines the current evidence supporting or refuting neoadjuvant therapy and discusses criteria for selecting patients who would derive significant benefit, along with proposing an optimal chemotherapy regimen for iGBC patients. Improved outcomes have been reported in patients undergoing reoperation after 4 to 14 weeks following the initial cholecystectomy compared to immediate reoperation. Limited, yet promising, evidence supports the use of 3 to 4 cycles of gemcitabine-based neoadjuvant chemotherapy prior to reoperative surgery in select high-risk iGBC cases.

Methods: This study included 41 patients with single-level grades 1 or 2 LS from February 2023 to February 2024. Clinical outcomes were assessed using the Visual Analog Scale (VAS) for back and leg pain and the Oswestry Disability Index (ODI). Bridwell fusion grades were evaluated via lumbar spine computed tomography performed 6 months postoperatively. Results: Over a mean follow-up period of 10.6 months (range, 7–18 months), significant improvements were observed in VAS scores for low back pain (from 7.8±0.8 to 2.1±1.4) and leg pain (from 8.1±1.3 to 1.9±1.5) as well as ODI scores (from 50.4±15.4 to 14.8±10.5). The cohort consisted of patients with grades 1 (73.2%) and 2 LS (26.8%) at L4–L5 (58.6%), L5–S1 (34.1%), and L3–L4 (7.3%) levels. The mean operation time was 182.8±36.4 minutes, with a mean intraoperative blood loss of 190.5±81.3 mL and a mean hospital stay of 7.2±3.6 days. Successful fusion (Bridwell grades I/II) was achieved in 82.9% of the cases, with a 4.9% incidence of cage subsidence. Minor complications included durotomies in two patients (4.9%), whereas no major complications, such as nerve root injury, hardware-related issues, or postoperative infections, were reported. Conclusions The described BE-LIF technique, using HA bone grafts, which are an autologous bone from the preserved IAP, and a TLIF cage, is a viable, safe, and effective option for treating low-grade LS. This approach achieves favorable clinical outcomes and high fusion rates, which provides a cost-effective alternative to advanced surgical implants.