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Background: Fluoroscopy-guided PTNB for fluoroscopy-identifiable lung lesions has been suggested as a useful method for the pathological diagnosis of lung lesions; however, it is lacking in accuracy and safety compared to CT-guided PTNB. Thus, we aimed to investigate the diagnostic accuracy and complications of fluoroscopy-guided percutaneous transthoracic needle biopsy (PTNB) with the aid of pre-procedural planning cone-beam computed tomography (CBCT) in order to take advantage of their respective strengths. Methods: A total of 255 fluoroscopy-guided PTNBs with the aid of planning CBCT were performed. Pre-procedural planning CBCT was conducted to calculate the shortest length from the skin puncture site to the margin of the target lesion for the needle trajectory. No intra-procedural CBCT was performed. The diagnostic performance of fluoroscopy-guided PTNB with the aid of planning CBCT was calculated. The prognostic factors for diagnostic failures and complications were evaluated using logistic regression analysis. Results: The accuracy, sensitivity, specificity, PPV, and NPV were 97.3%, 88.0%, 90.9%, 100%, and 62.5%, respectively. There were 29 diagnostic failures (11.8%), and the multivariable analysis showed that a longer lesion depth on CBCT and a shorter specimen length were each associated with diagnostic failure (p = 0.010 and 0.012, respectively). Complications occurred in 34 PTNBs (13.3%). The multivariable analysis showed that an increased total number of biopsies per lesion, a longer length of lung aeration via needle insertion, a smaller lesion size on CT imaging (≤20 mm), and the presence of an air bronchogram were associated with the occurrence of complications (p = 0.027, <0.001, 0.003, and 0.020, respectively). Conclusions: Excellent diagnostic accuracy was obtained by fluoroscopy-guided PTNB with the aid of planning CBCT. Compared to that of CT- or CBCT-guided PTNB, the procedure-related complication rate was acceptably low, but the radiation dose to patients could be potentially reduced. [ABSTRACT FROM AUTHOR]

Thromboembolic disorders, arising from abnormal coagulation, pose a significant risk to human life in the modern world. The FDA has recently approved several anticoagulant drugs targeting factor Xa (FXa) to manage these disorders. However, these drugs have potential side effects, leading to bleeding complications in patients. To mitigate these risks, coagulation factor IXa (FIXa) has emerged as a promising target due to its selective regulation of the intrinsic pathway. Due to the high structural and functional similarities of these coagulation factors and their inhibitor binding modes, designing a selective inhibitor specifically targeting FIXa remains a challenging task. The dynamic behavior of protein–ligand interactions and their impact on selectivity were analyzed using molecular dynamics simulation, considering the availability of potent and selective compounds for both coagulation factors and the co-crystal structures of protein–ligand complexes. Throughout the simulations, we examined ligand movements in the binding site, as well as the contact frequencies and interaction fingerprints, to gain insights into selectivity. Interaction fingerprint (IFP) analysis clearly highlights the crucial role of strong H-bond formation between the ligand and D189 and A190 in the S1 subsite for FIXa selectivity, consistent with our previous study. This dynamic analysis also reveals additional FIXa-specific interactions. Additionally, the absence of polar interactions contributes to the selectivity for FXa, as observed from the dynamic profile of interactions. A contact frequency analysis of the protein–ligand complexes provides further confirmation of the selectivity criteria for FIXa and FXa, as well as criteria for binding and activity. Moreover, a ligand movement analysis reveals key interaction dynamics that highlight the tighter binding of selective ligands to the proteins compared to non-selective and inactive ligands. [ABSTRACT FROM AUTHOR]

Recently, academic and industrial scientific communities involved in kinetics-based drug development have become immensely interested in predicting the drug target residence time. Screening drug candidates in terms of their computationally predicted residence times, which is a measure of drug efficacy in vivo, and simultaneously assessing computational binding affinities are becoming inevitable. Non-equilibrium molecular simulation approaches are proven to be useful in this purpose. Here, we have implemented an optimized approach of combining the data derived from steered molecular dynamics simulations and the Bell-Evans model to predict the absolute residence times of the antagonist ZMA241385 and agonist NECA that target the A2A adenosine receptor of the G-protein-coupled receptor (GPCR) protein family. We have predicted the absolute ligand residence times on the timescale of seconds. However, our predictions were many folds shorter than those determined experimentally. Additionally, we calculated the thermodynamics of ligand binding in terms of ligand binding energies and the per-residue contribution of the receptor. Subsequently, binding pocket hotspot residues that would be important for further computational mutagenesis studies were identified. In the experiment, similar sets of residues were found to be in significant contact with both ligands under study. Our results build a strong foundation for further improvement of our approach by rationalizing the kinetics of ligand unbinding with the thermodynamics of ligand binding. [ABSTRACT FROM AUTHOR]

Background: We investigated the patterns and timing of recurrence and death as well as prognostic factors based on clinicopathological and radiological factors in patients who underwent surgical treatment for invasive mucinous adenocarcinoma (IMA). Methods: We reviewed clinicopathological findings including spread through air spaces (STAS) and CT findings of IMA such as morphology, solidity, margin, well-defined heterogeneous ground-glass opacity, CT angiogram, and air bronchogram signs from 121 consecutive patients who underwent surgical resection. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified. Hazard rate analyses were performed for the survival dynamics. Results: T stage (hazard ratio [HR] = 4.102, p = 0.03), N stage (N2 vs. N0, HR = 7.653, p < 0.001), and consolidative CT morphology (HR = 3.556, p = 0.008) remained independent predictors for DFS. Age (HR = 1.110, p = 0.002), smoking (HR = 12.893, p < 0.001), T stage (HR = 13.005, p = 0.006), N stage (N2 vs. N0, HR = 7.653, p = 0.004), STAS (HR = 7.463, p = 0.008), and consolidative CT morphology (HR = 6.779, p = 0.007) remained independent predictors for OS. Consolidative morphology, higher T and N stage, and presence of STAS revealed initial sharp peaks after steep decline of the hazard rate curves for recurrence or death in follow-up period. Conclusions: Consolidative morphology, higher T and N stage, smoking, and STAS were indicators of significantly greater risk of early recurrence or death in patients with IMA. Thus, these findings could be incorporated into future surveillance strategies. [ABSTRACT FROM AUTHOR]

Background: Because shape or irregularity along the tumor perimeter can result from interactions between the tumor and the surrounding parenchyma, there could be a difference in tumor growth rate according to tumor margin or shape. However, no attempt has been made to evaluate the correlation between margin or shape features and tumor growth. Methods: We evaluated 52 lung adenocarcinoma (ADC) patients who had at least two computed tomographic (CT) examinations before curative resection. Volume‐based doubling times (DTs) were calculated based on CT scans, and patients were divided into two groups according to the growth pattern (GP) of their ADCs (gradually growing tumors [GP I] vs. growing tumors with a temporary decrease in DT [GP II]). CT radiomic features reflecting margin characteristics were extracted, and radiomic features reflective of tumor DT were selected. Results: Among the 52 patients, 41 (78.8%) were assigned to GP I and 11 (21.2%) to GP II. Of the 94 radiomic features extracted, eccentricity, surface‐to‐volume ratio, LoG uniformity (σ = 3.5), and LoG skewness (σ = 0.5) were ultimately selected for tumor DT prediction. Selected radiomic features in GP I were surface‐to‐volume ratio, contrast, LoG uniformity (σ = 3.5), and LoG skewness (σ = 0.5), similar to those for total subjects, whereas the radiomic features in GP II were solidity, energy, and busyness. Conclusions: This study demonstrated the potential of margin‐related radiomic features to predict tumor DT in lung ADCs. Key points: Significant findings of the study: We found a relationship between margin‐related radiomic features and tumor doubling time. What this study adds: Margin‐related radiomic features can potentially be used as noninvasive biomarkers to predict tumor doubling time in lung adenocarcinoma and inform treatment strategies. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that the efficacy of immunotherapy in non-small cell lung cancers (NSCLCs) is associated with the immune microenvironment within the tumor. We aimed to explore radiologic phenotyping using a radiomics approach to assess the immune microenvironment in NSCLC. Two independent NSCLC cohorts (training and test sets) were included. Single-sample gene set enrichment analysis was used to determine the tumor microenvironment, where type 1 helper T (Th1) cells, type 2 helper T (Th2) cells, and cytotoxic T cells were the targets for prediction with computed tomographic (CT) radiomic features. Multiple algorithms were in the modeling followed by final model selection. The training dataset comprised 89 NSCLCs and the test set included 60 cases of lung squamous cell carcinoma and adenocarcinoma. A total of 239 CT radiomic features were used. A linear discriminant analysis model was selected for the final model of Th2 cell group prediction. The area under the curve value of the final model on the test set was 0.684. Predictors of the linear discriminant analysis model were skewness (total and outer pixels), kurtosis, variance (subsampled from delta [subtraction inner pixels from outer pixels]), and informational measure of correlation. The performances of radiomics on test set of Th1 and cytotoxic T cell were not accurate enough to be predictable. A radiomics approach can be used to interrogate an entire tumor in a noninvasive manner and provide added diagnostic value to identify the immune microenvironment of NSCLC, in particular, Th2 cell signatures. [ABSTRACT FROM AUTHOR]

Since the thermal environment of large space buildings such as stadiums can vary depending on the location of the stands, it is important to divide them into different zones and evaluate their thermal environment separately. The thermal environment can be evaluated using physical values measured with the sensors, but the occupant density of the stadium stands is high, which limits the locations available to install the sensors. As a method to resolve the limitations of installing the sensors, we propose a method to predict the thermal environment of each zone in a large space. We set six key thermal factors affecting the thermal environment in a large space to be predicted factors (indoor air temperature, mean radiant temperature, and clothing) and the fixed factors (air velocity, metabolic rate, and relative humidity). Using artificial neural network (ANN) models and the outdoor air temperature and the surface temperature of the interior walls around the stands as input data, we developed a method to predict the three thermal factors. Learning and verification datasets were established using STAR CCM+ (2016.10, Siemens PLM software, Plano, TX, USA). An analysis of each model's prediction results showed that the prediction accuracy increased with the number of learning data points. The thermal environment evaluation process developed in this study can be used to control heating, ventilation, and air conditioning (HVAC) facilities in each zone in a large space building with sufficient learning by ANN models at the building testing or the evaluation stage. [ABSTRACT FROM AUTHOR]

To examine the levels of antipolymer antibody (APA) in Korean female patients with fibromyalgia (FM) and to determine whether the levels of APA correlate with FM severity. Serum samples from patients with FM ( n = 69), patients with rheumatoid arthritis (RA) ( n = 71), and controls ( n = 75) were assayed for APA. All of the subjects were female, and the controls were age-matched healthy volunteers. FM tender point counts and scores were examined, and FM patients were asked to complete a Korean version of the Fibromyalgia Impact Questionnaire (FIQ), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). APA-positive samples were detected in five (7.2%) of the 69 FM patients, seven (9.9%) of the 71 RA patients, and four (5.3%) of the 75 controls. The prevalence of seropositivity and the level of APA in FM patients did not differ from those in RA patients and controls. The proportion positive for APA was not higher for FM patients with severe symptoms than for FM patients with mild symptoms. There was a negative association between the APA level and age. The APA level in FM patients was not correlated with age at diagnosis, age at symptom onset, disease duration, education, tender point counts and scores, FIQ, STAI, or BDI. The prevalence of APA in Korean FM patients was quite low. Owing to the low prevalence of APA in this study, the APA assay did not distinguish FM patients with severe symptoms from those with mild symptoms. [ABSTRACT FROM AUTHOR]

Purpose: To compare the image quality of brain computed tomography (CT) images reconstructed with deep learning–based image reconstruction (DLIR) and adaptive statistical iterative reconstruction-Veo (ASIR-V). Methods: Sixty-two patients underwent routine noncontrast brain CT scans and datasets were reconstructed with 30% ASIR-V and DLIR with three selectable reconstruction strength levels (low, medium, high). Objective parameters including CT attenuation, noise, noise reduction rate, artifact index of the posterior cranial fossa, and contrast-to-noise ratio (CNR) were measured at the levels of the centrum semiovale and basal ganglia. Subjective parameters including gray matter-white matter differentiation, sharpness, and overall diagnostic quality were also assessed and compared with the interobserver agreement. Results: There was a gradual reduction in the image noise and artifact index of the posterior cranial fossa as the strength levels of DLIR increased (all P < 0.001) compared with that of ASIR-V. CNR in both the centrum semiovale and basal ganglia levels also improved from the low to high strength levels of DLIR compared with that of ASIR-V (all P < 0.001). DLIR images with medium and high strength levels demonstrated the best subjective image quality scores among the reconstruction datasets. There was moderate to good interobserver agreement for the subjective image quality assessments with ASIR-V and DLIR. Conclusion: On routine brain CT scans, optimized protocols with DLIR allowed significant reduction of noise and artifacts with improved subjective image quality compared with ASIR-V. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the clinical courses and outcomes of patients with monoarthritis and to investigate the predictive factors of clinical outcomes. Methods A retrospective analysis was performed of 171 patients with chronic monoarthritis at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics, radiographic findings and the clinical course were reviewed. Results The most commonly involved joints were the knees (24.0%), followed by the wrists (22.8%) and ankles (18.7%). A final diagnosis was established in 74 (43.3%) patients. Thirty-one (18.1%) patients were diagnosed with rheumatoid arthritis ( RA), 23 (13.5%) with peripheral spondyloarthritis (SpA), and 19 (11.1%) with Behçet's disease ( BD). Among 108 patients who were initially undiagnosed, 85 (78.7%) patients remained with undiagnosed monoarthritis, with relatively shorter symptom durations and requiring less treatment. The initially involved joint was a predictive factor for the final diagnosis: the wrist joint for RA (odds ratio [ OR] 11.58, P < 0.001), the ankle joint for SpA ( OR 6.19, P < 0.001), and the knee joint for BD ( OR 3.43, P = 0.014). Bony erosion at baseline was associated with progression to oligo- or polyarthritis ( OR 2.88, P = 0.030) and with radiographic progression. Conclusions In patients presenting with monoarthritis, a final diagnosis was established in less than half of the patients, and a majority of undiagnosed patients showed benign clinical courses. The initially involved joint and the presence of erosion at baseline were predictors of the final diagnosis and of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Stenotrophomonas maltophilia (S. maltophilia) is a globally emerging, rare, waterborne, aerobic, gram-negative, multiple-drug-resistant organism, most commonly associated with respiratory tract infection in humans. Computed tomography (CT) findings in patients with S. maltophilia pneumonia are rarely reported.Purpose: To compare CT findings between immunocompromised and immunocompetent patients, and to determine characteristic imaging findings of S. maltophilia pneumonia.Material and Methods: CT findings of eight immunocompromised and 29 immunocompetent patients with proven S. maltophilia pneumonia were reviewed retrospectively. Different patterns of CT abnormalities between immunocompromised and immunocompetent patients were compared by Fisher's exact test.Results: Patchy ground-glass opacities (GGOs) were the most common CT findings, present in 36 (97.3%) of the 37 patients. Among the patients with patchy GGOs, consolidation was seen in 29 (78.4%) patients, and centrilobular nodules were noted in 15 (40.5%) patients. The transaxial distribution of the parenchymal abnormalities was predominantly randomly distributed in 30 (81.1%) cases. Regarding longitudinal plane involvement, the predominant zonal distributions were the diffuse distribution (n=23, 62.2%) and the lower lung zone (n=14, 37.8%). None of the patients showed upper lung zone predominance. The proportion of patients with parenchymal CT findings or associated findings in the immunocompromised patients was not significantly different from that of the immunocompetent patients. However, lower lung zone predominance on the longitudinal plane was significantly more common in immunocompetent patients than in immunocompromised patients (14/29 vs. 0/8, P=0.015). And diffuse distribution of parenchymal abnormalities on a longitudinal plane was significantly more frequent in immunocompromised patients than in immunocompetent patients (8/8 vs. 15/29, P=0.015).Conclusion: The most common CT patterns of S. maltophilia pneumonia in immunocompromised and immunocompetent patients were patchy GGOs and consolidation. However, in immunocompetent patients, parenchymal abnormalities were more predominately distributed in lower lung zone than in immunocompromised patients; and in immunocompromised patients, parenchymal abnormalities were more diffusely distributed than in immunocompetent patients. [ABSTRACT FROM AUTHOR]

Background. Although many Koreans travel each year to countries where malaria is present, few data are available on the knowledge, attitudes, and practices of Koreans with regards to malaria. Methods. The study was conducted in the departure lounge of Incheon International Airport in May 2006. A 22-item questionnaire was administered to Korean travelers whose travel destination was India. Results. Of 188 respondents, 24% had sought pretravel health information. Independent predictors for seeking pretravel health information were the following: being a Korean woman, longer duration of travel, planning to travel independently or to a rural area, and perceived risk of malaria. A total of 47% of travelers answered that they had not perceived any risk of malaria, and only 7% of travelers carried malaria prophylaxis. Conclusions. There is an urgent need for increased awareness about travel-related infectious diseases (especially malaria) among Korean travelers, and they should be encouraged to seek pretravel health information. [ABSTRACT FROM AUTHOR]