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Poly(dimethylsiloxane) (PDMS) was grafted onto polyurethane (PU), and Epichlorohydrin and Bisphenol A were attached to the free ends of PDMS groups and used to link the grafted PDMS to thereby introduce flexible crosslinks between the PU chains. The flexible crosslinks enhanced the crosslink density and solution viscosity of PU but did not change the melting and crystallization behaviors of the soft segments of PU. In particular, the flexible PDMS crosslinks increased the maximum tensile stress by up to 300% and the maximum tensile strain up to 180%. The shape recovery capability at 10°C and the shape retention capability at −25°C were maintained above 90% with the flexible crosslinking. Grafted PDMS moderately improved the low-temperature flexibility of PU due to its flexibility at low temperature. The flexible crosslinks of grafted PDMS successfully improved the tensile strength, shape recovery, and low-temperature flexibility of the PU.

Automated vehicles (AVs) are believed to have great potential to improve the traffic capacity and efficiency of the current transport systems. Despite positive findings of the impact of AVs on traffic flow and potential road capacity increase for highways, few studies have been performed regarding the impact of AVs on urban roads. Moreover, studies considering traffic volume increase with a mixture of AVs and human-driven vehicles (HDVs) have rarely been conducted. Therefore, this study investigated the impact of gradual increments of AV penetration and traffic volume on urban roads. The study adopted a microsimulation approach using VISSIM with a Wiedmann 74 model for car-following behavior. Parameters for AVs were set at the SAE level 4 of automation. A real road network was chosen for the simulation having 13 intersections in a total distance of 4.5 km. The road network had various numbers of lanes from a single lane to five lanes in one direction. The network consists of a main arterial road and a parallel road serving nearby commercial and residential blocks. In total, 36 scenarios were investigated by a combination of AV penetrations and an increase in traffic volumes. The study found that, as AV penetration increased, traffic flow also improved, with a reduction of the average delay time of up to 31%. Also, as expected, links with three or four lanes had a more significant impact on the delay. In terms of road capacity increase, when the penetration of AVs was saturated at 100%, the road network could accommodate 40% more traffic.

Melamine was grafted to a polyurethane (PU) frame and utilized for cross-linking PU via amino groups. The degree of crosslinking and the solution viscosity increased notably after grafting melamine due to the formation of crosslinks. The thermal transition of the soft segment was not significantly affected, but the glass transition was observed at a slightly higher temperature in case of the grafted melamine. Melamine-mediated crosslinking increased not only the breaking tensile stress but also the shape recovery performance of PU. In addition, crosslinked PU was more flexible at low temperature than unmodified PU. Overall, melamine-mediated crosslinking improved the tensile resistance to stress, the recovery tendency to the initial shape, and the flexibility with minor changes in the thermal transition, tensile strain, and shape retention at a low temperature.

A substantial amount of research effort has been directed toward the development of Pt-based catalysts with higher performance and durability than conventional polycrystalline Pt nanoparticles to achieve high-power and innovative energy conversion systems. Currently, attention has been paid toward expanding the electrochemically active surface area (ECSA) of catalysts and increase their intrinsic activity in the oxygen reduction reaction (ORR). However, despite innumerable efforts having been carried out to explore this possibility, most of these achievements have focused on the rotating disk electrode (RDE) in half-cells, and relatively few results have been adaptable to membrane electrode assemblies (MEAs) in full-cells, which is the actual operating condition of fuel cells. Thus, it is uncertain whether these advanced catalysts can be used as a substitute in practical fuel cell applications, and an improvement in the catalytic performance in real-life fuel cells is still necessary. Therefore, from a more practical and industrial point of view, the goal of this review is to compare the ORR catalyst performance and durability in half- and full-cells, providing a differentiated approach to the durability concerns in half- and full-cells, and share new perspectives for strategic designs used to induce additional performance in full-cell devices.

Background We aimed to investigate the detection rate of body CT or PET/CT for sites of extracranial disease in patients with a new pathological diagnosis of CNS DLBCL and to identify factors associated with sites of extracranial disease. Methods An international multicenter cohort study of consecutive immunocompetent patients with a new diagnosis of CNS DLBCL confirmed by brain biopsy who underwent CT and/or PET/CT to evaluate for sites of extracranial disease between 1998 and 2019. The primary outcome was the detection rate of extracranial lymphoma by CT or PET/CT. Subgroup analyses according to age and EBV status were also performed. Logistic regression analyses were performed to determine factors related to sites of extracranial disease. Detection rates of CT and PET/CT were compared. Results One thousand and forty-three patients were included. The overall detection rate of CT or PET/CT was 2.6% (27/1043). The treatment approach was adjusted in 74% of these patients. Multivariable analysis demonstrated that age >61 years (OR, 3.10; P = .016) and EBV positivity (OR, 3.78; P = .045) were associated with greater odds of extracranial lymphoma. There was no statistically significant difference in detection rate between CT and PET/CT (P = .802). In patients ≤61 years old, the false-referral rates were significantly higher than the detection rates (P < .001). Conclusion Our results showed increased odds of extracranial lymphoma in patients with older age or EBV-positive lymphoma. Treatment was adjusted in a majority of patients diagnosed with extracranial lymphoma, thereby supporting the current guidelines for the use of contrast-enhanced body CT or PET/CT in patients with newly diagnosed CNS DLBCL.

To evaluate the association between thyroid echogenicity and heterogeneity seen on ultrasonography (US) and thyroid function in pediatric and adolescent populations with autoimmune diffuse thyroid diseases (AITD). From 2000 to 2020, we reviewed thyroid ultrasound (US) images and thyroid function statuses in 133 children and adolescent AITD patients. Our review of the images focused on decreased echogenicity and heterogeneity, which were classified into four grades. Among patients with overt hypothyroidism or overt hyperthyroidism, 94.2% (65/69) showed a US grade of 3 or 4. In patients with subclinical hyper/hypothyroidism or euthyroidism, 45.3% (29/64) showed grades 1 or 2. There were no overt hyper/hypothyroidism patients with US grade 1. When we compared US grades according to thyroid status, more severe thyroid dysfunction was significantly associated with higher US grade (p = 0.047). Thyroid stimulating hormone (TSH) level differed significantly according to US grades when we evaluated hyperthyroid (p = 0.035) and hypothyroid (p = 0.027) states independently. 11 patients showed both US grade and thyroid function status changes on follow-up US. In children and adolescent AITD patients, there was an association between decreased echogenicity and heterogeneity on US and thyroid dysfunction.

BACKGROUND Regular self-administered exercise after stroke can improve upper limb function. For proper self-administered exercise, an appropriate guide is required to match the exercise level to the patient’s upper limb disability. OBJECTIVE This study aimed to develop a mobile health application to support self-administered graded upper limb exercises for patients with hemiplegia using deep learning model. METHODS To develop a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, we used a 5-step design thinking process. The exercise programs in the application were safe and easy to follow in the sitting position. A deep learning model was proposed to automatically evaluate the patients’ upper limb function for recommendation of exercise according to each patient’s disability. The model captured videos of patients reaching and grasping objects on a table as input and predicted the exercise level. Potential end-users, including patients, therapists, and physicians, evaluated the prototype and provided feedback for the usability and quality of the application using a mobile application rating scale. RESULTS A total of six features, my information, evaluation section, daily exercise, list of exercises, my current exercise status, and notification, were incorporated into the mobile application. The application consisted of 58 exercises categorized as postural and balance, range of motion, strengthening, and task-oriented training exercises with three levels of difficulty. A deep-learning-based model was proposed for automated upper limb function evaluation. The overall accuracy of classification of exercised level was 84.58% and inference time was 9~10 seconds. CONCLUSIONS We successfully developed a mobile application to support self-administered graded upper limb exercises for patients with hemiplegia based on individual ability, including automatic evaluation using a deep learning model.

Background: For an objective and quantitative evaluation for videofluosroscopic swallowing study (VFSS), temporal parameters during swallowing are analyzed for both clinical and research purposes. However, because it is time-consuming and is complicated to analyze manually by clinicians, automated analysis using deep learning has been attempted. This study aimed to develop a model for automatic measurement of various temporal parameters of swallowing using deep learning. Methods: Five-hundred and forty-seven VFSS video clips were included in this study. Seven temporal parameters were manually measured by two physiatrists as ground-truth data: oral phase duration, pharyngeal delay time, pharyngeal response time, pharyngeal transit time, laryngeal vestibule closure reaction time, laryngeal vestibule closure duration and upper esophageal sphincter opening duration. ResNet3D was chosen as the base model for deep learning of temporal parameters. Specifically, we proposed several architectural variants of ResNet3D to improve the estimation of temporal parameters. The performance of ResNet3D variants was compared with that of the VGG and I3D models which were used in the previous studies. Results: The average accuracy of the proposed ResNet3D variants in measuring the temporal parameter of VFSS was from 0.864 to 0.981. F1 score ranged from 0.707 to 0.924, and average precision ranged from 0.643 to 0.865. In comparison with the VGG and I3D models, our model achieved the best results in terms of accuracy, F1 score and average precision values. Conclusion: We proposed deep learning models for automatically measuring temporal parameters of VFSS. The proposed ResNet3D variants outperformed the existing models in detecting all phases of the swallowing process. Through the clinical application of this automatic model,, temporal analysis of VFSS will be easier and more accurate.

Background The purpose of this study was to investigated whether a specific subtype of the newly proposed Korean Medicine (KM) phenotype could support as a risk to metabolic syndrome (MetS). Methods A dataset of 1997 subjects were used from the Korean Medicine Daejeon Citizen Cohort. To extract the KM phenotype of the participants, questionnaires of sasang constitutional types (SCTs) and cold-heat pattern identification (CHPI) were adopted; correlations with KM phenotype were assessed using Cramer's V test. Odds ratios and the area under the curve (AUC) were used to evaluate the performance of the MetS classification models on the basis of the proposed KM phenotype, single type of SCTs, and single type of CHPI. Results This study included 179 and 1,818 participants in the MetS and non-MetS group, respectively (MetS prevalence rate of 8.96%); the participants’ mean ages were 46.45 and 44.12 years (p

Adequate clinical evaluation of artificial intelligence (AI) algorithms before adoption in practice is critical. Clinical evaluation aims to confirm acceptable AI performance through adequate external testing and confirm the benefits of AI-assisted care compared with conventional care through appropriately designed and conducted studies, for which prospective studies are desirable. This article explains some of the fundamental methodological points that should be considered when designing and appraising the clinical evaluation of AI algorithms for medical diagnosis. The specific topics addressed include the following

Purpose NKG2A, an inhibitory receptor expressed on NK cells and T cells, leads to immune evasion by binding to HLA-E expressed on cancer cells. Here, we investigated the relationship between HLA-E surface expression on head and neck squamous cell carcinoma (HNSCC) cell lines and the efficacy of monalizumab, an NKG2A inhibitor, in promoting NK cell activity. Methods Six HNSCC cell lines were used as target cells. After exposure to IFN- γ, HLA-E surface expression on HNSCC cell lines was measured by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy donors and isolated NK cells were used as effector cells. NK cells were stimulated by treatment with IL-2 and IL-15 for 5 days, and NK cell-induced cytotoxicity was analyzed by CD107a degranulation and51Cr release assays. Results We confirmed that HLA-E expression was increased by IFN-γ secreted by NK cells and that HLA-E expression was different for each cell line upon exposure to IFN-γ. Cell lines with high HLA-E expression showed stronger inhibition of NK cell cytotoxicity, and efficacy of monalizumab was high. Combination with cetuximb increased the efficacy of monalizumab. In addition, stimulation of isolated NK cells with IL-2 and IL-15 increased the efficacy of monalizumab, even in the HLA-E low groups. Conclusion Monalizumab efficacy was correlated with HLA-E surface expression and was enhanced when NK cell activity was increased by cetuximab or cytokines. These results suggest that monalizumab may be potent against HLA-E-positive tumors and that monalizumab efficacy could be improved by promoting NK cell activity.

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with frequent metastasis and high mortality in the oral cavity. Plant-derived natural compounds are actively progressing as a trend for cancer treatment. Latifolin (Latif), is a natural flavonoid isolated from the heartwood of Dalbergia odorifera T. Chen (D. odorifera) has been known to have beneficial effects on anti-aging, anti-carcinogenic, anti-inflammatory, and cardio-protective activities. However, the anti-cancer effects of Latif are unknown in OSCC. Herein, as a result of analysis in terms of the aggressive features of OSCCs, we found that Latif significantly inhibited the cell proliferation of human YD-8 and YD-10B OSCCs, and caused the anti-metastatic activities by effectively blocking cell migration, invasion, and adhesion via the inactivation of focal adhesion kinase (FAK)/non-receptor tyrosine kinase (Src). Moreover, we found that Latif induced apoptotic cell death to suppress the cell survival and proliferation of YD-10B OSCCs by targeting PI3K/AKT/mTOR/p70S6K signaling. Finally, we analyzed in terms of autophagy and necroptosis, which are other mechanisms of programmed cell death and survival compared to apoptosis in YD-10B OSCCs. We found that Latif suppressed autophagic-related proteins and autophagosome formation, and also Latif inhibited necroptosis by dephosphorylating necroptosis-regulatory proteins (RIP1, RIP3, and MLKL). Given these findings, our results provided new evidence for Latif’s biological effect and mechanism in YD-10B OSCCs, suggesting that Latif may be a new candidate for patients with OSCCs.

Purpose: Magnetic resonance imaging (MRI) is a useful tool for evaluating brain injury and maturation in preterm infants and often requires sedation to acquire images of sufficient quality. Infant sedation is often associated with adverse events, despite extreme precautions. In this study, the swaddling technique was investigated as an alternative non-pharmacological strategy to obtain brain MRIs of sufficient quality.Methods: We applied the feed and swaddle technique during routine brain MRI as a quality improvement project and compared its morbidity with that of sedation in a historic age-matched group. Seventy-nine very low birth weight infants in the neonatal intensive care unit of Ajou University Hospital (Suwon, Korea) were enrolled. Thirty-two (40.5%) infants were in the feed and swaddling group, and 47 (59.5%) were in the sedation group.Results: The morbidity associated with the cardiopulmonary system (swaddling group vs. sedation group: 53.13% [n=17] vs. 63.83% [n=30], P=0.723) and central nervous system (40.63% [n=13] vs. 29.79% [n=14], P=0.217) were not significantly different between groups. The MRI failure rate was not significantly different (swaddling group vs. sedation group: 12.5% [n=4] vs. 4.3% [n=2], P=0.174). The MRI scanning time was longer in the swaddling group than in the sedation group (76.5±20.3 minutes vs. 61.5±13.6 minutes, P=0.001). Cardiopulmonary adverse events were significantly less common in the swaddling group than in the sedation group (3.13% [n=1] vs. 34.04% [n=16], P=0.002).Conclusion: The success rate of MRI was comparable between the swaddling technique and sedation. Furthermore, despite the drawback of prolonged scan time, cardiopulmonary adverse events are fewer with swaddling than with sedative agents. Therefore, swaddling can be an alternative to sedation or anesthesia when performing neonatal MRI scans.

The phase I trial is the first step in administering a drug to humans, but it has no therapeutic purpose. Under the absence of therapeutic purpose, healthy volunteers demonstrated different motivations, unlike the actual patients participating in trials. There were many reported motivations, such as financial motivation, contributing to the health science, accessing ancillary health care benefits, scientific interest or interest in the goals of the study, meeting people, and general curiosity. The aim of this study was to identify the motivation and characteristics of healthy volunteers participating in phase I trials in the Republic of Korea. We gave surveys to 121 healthy volunteers to study their demographic characteristics and the reasons of participation. We identified whether the decision to participate in the research was influenced by demographic factors and whether the perception and attitudes toward the research were influenced by the characteristics of the healthy volunteers. After completion of the first survey, 12 healthy volunteers who had participated in a phase I clinical trial were selected to answer the second interview. According to our survey, most healthy volunteers were unmarried men and economically dependent. Most of them participated in the study because of financial reward. The most important factor to measure financial reward was the research period. Also, 43% of the volunteers were university students, 42% answered “university graduation” and 55% were residing in family-owned houses. Many healthy volunteers were found to be living in family homes and to have a student status or lack of economic independence. Results of the survey showed that 64% of respondents indicated having more than one clinical trial participation. In-depth interviews showed that healthy volunteers had diverse motivation to participate in research and that healthy volunteer perceive the clinical trial positively. The main motivation for healthy volunteers’ participation in research was “financial reward.” Healthy volunteers also considered research schedules, processes, and safety, and had a positive perception of clinical trials, but they thought that the public has a negative perception.

From May 2015 to June 2016, data on 296 patients undergoing 1.5-Tesla MRI for symptoms of acute ischemic stroke were retrospectively collected. Conventional, echo-planar imaging (EPI) and echo train length (ETL)-T2-FLAIR were simultaneously obtained in 118 patients (first group), and conventional, ETL-, and repetition time (TR)-T2-FLAIR were simultaneously obtained in 178 patients (second group). A total of 595 radiomics features were extracted from one region-of-interest (ROI) reflecting the acute and chronic ischemic hyperintensity, and concordance correlation coefficients (CCC) of the radiomics features were calculated between the fast scanned and conventional T2-FLAIR for paired patients (1st group and 2nd group). Stabilities of the radiomics features were compared with the proportions of features with a CCC higher than 0.85, which were considered to be stable in the fast scanned T2-FLAIR. EPI-T2-FLAIR showed higher proportions of stable features than ETL-T2-FLAIR, and TR-T2-FLAIR also showed higher proportions of stable features than ETL-T2-FLAIR, both in acute and chronic ischemic hyperintensities of whole- and intersection masks (p

Purposes: Immune checkpoint inhibitors (ICIs) markedly improve the clinical outcomes of advanced non-small-cell lung cancer (NSCLC). However, the intracranial efficacy of ICI is not well elucidated, and previous studies showed discordant outcomes of ICI between intracranial and extracranial diseases. We aimed to evaluate the clinical outcomes and the intracranial and extracranial response of patients with NSCLC and brain metastasis who were treated with ICI in the real-world setting. Methods: A total of 55 patients (median age, 63 years [range, 42–80]; male, 78%) who had NSCLC with brain metastasis and treated with ICI monotherapy were retrospectively analyzed. We separately assessed the response rates of brain lesions and systemic lesions, and estimated the overall survival (OS) and progression-free survival (PFS). Results: The median OS and overall PFS were 17.0 months (95% CI, 10.3–25.6) and 3.19 months (95% CI, 2.24-5.03), respectively. The intracranial objective response rate and disease control rate of ICI were 36% and 54%, respectively. Among the 44 patients who showed disease progression, only 32% (n = 14) showed concordant outcomes and 9 patients (20%) showed opposing discordant outcomes. Eight patients continued ICI with local brain therapy after intracranial progression, and their median extracranial PFS and OS were 15 months (95% CI, 5.0–not assessed [NA]) and 23.8 months (95% CI, 14.7–NA), respectively. Conclusions: ICI monotherapy had a clinically meaningful intracranial efficacy in NSCLC patients with brain metastasis. Watchful waiting and close monitoring without local radiotherapy might be feasible in NSCLC patients with asymptomatic active brain metastasis.

Differential leukocyte counts of pleural fluid are routinely recommended for the early diagnosis and management of exudative pleural effusions. Rapid automated cellular analysis agrees strongly with standard manual microscopic counts and has become a reality in many clinical laboratories. However, discordant results sometimes observed between automated and manual analyses raise concern about using automated analysis to aid prompt differential diagnosis. This study aimed to evaluate the real-world disagreement between automated and manual leukocyte analyses in exudative pleural effusions and to investigate whether the discordant results occur in specific cellular ranges or randomly. We conducted a retrospective study of patients who were diagnosed with parapneumonic pleural effusions (PPE), tuberculous pleural effusions (TPE), and malignant pleural effusions (MPE) between September 2018 and December 2020. Differential and predominant leukocyte counts were performed using an automated XN-350 analyzer with a two-part differential count consisting of polymorphonuclear (PMN) and mononuclear (MN) leukocytes and a manual method with Wright-stained cytospin slides. We compared the two methods on cases of 109 PPEs, 50 TPEs, and 116 MPEs. Although the overall correlation between the two methods for differential leukocyte counts was excellent, there were etiologic variations; MPEs showed a lower correlation compared to PPEs and TPEs. Automated-PMN predominance almost corresponded to manual cytospin-neutrophilic predominance. In contrast, ~10% of the automated-MN predominance did not correspond with the cytospin-lymphocytic predominance. These discrepancies occurred most in the automated-MN% range of 51% to 60%, followed by 61% to 70%. The PMN% range ≥50% and30% on the automated analysis reliably corresponds to the neutrophilic and lymphocytic predominance, respectively. However, the MN% range of 51% to 70% may not coincide with lymphocytic predominance on manual cytospin analysis. This range leaves the potential cause of exudative pleural effusions open.

The Nordic Seas have been widely implicated by deep water formation as a part of Atlantic Meridional Overturning Circulation. This study explores the spatiotemporal variations in the near-surface salinity over the Nordic Seas associated with surface freshening factors by using monthly TOPAZ4 reanalysis data from 1991 to 2019. We first show that reliability of TOPAZ4 data compared to the salinity products of other reanalysis data, satellite data, and in-situ measurements in the Nordic Seas. The salinity variability was larger in the Greenland Sea (GS) than in the Norwegian Sea (NS) on both time scales of seasonal and interannual. The seasonal change of GS salinity was coincident with the seasonality of sea ice extent. The longer-time variations are decomposed by empirical orthogonal function (EOF) analysis. The GS salinity is mainly affected by current advection (29%) and sea ice extent (11%). The interannual response of salinity to the sea ice extent over the GS differs by season. NS salinity variability responds to the strength of the Subpolar Gyre associated with a large-scale atmospheric system that caused the freshening event in the mid-1990s. The propagation of the northward Atlantic Water core is observed over the period of about 3 years from the Faroe Shetland Channel to the Fram Strait at a speed of 2.6-6.5° year-1. Other freshening factors such as sea ice export from the Arctic, freshwater flux at the Fram Strait, and net precipitation are also discussed. For the past three decades, the continuous trend appeared only in the sea ice extent, which might be a signal of climate changes over high latitude. However, there was no significant trend other than the periodic change in a few years to the decadal time scale in the salinity of GS and NS. As preconditioning for deep convection, near-surface salinity within Greenland Sea Gyre was influenced by salinity fluctuation in both GS and NS.

Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small-cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (P = 0.04 and P = 0.04, respectively). The SNPrs11265375C>T in nescient helix-loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (P = 0.04 and P = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (P = 4 × 10-6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (P = 0.001). These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.

Hemoptysis is a common cause of emergency department (ED) visits. There is little data about the role of systemic hypertension as a cause of hemoptysis. The aim of this study was to evaluate the association between systemic blood pressure and the unknown etiology of hemoptysis. This retrospective study included consecutive patients who visited the ED owing to hemoptysis and underwent a chest computed tomography between January 2011 and June 2021. Details of the initial blood pressure at the ED visit were compared between two groups with identified and unidentified causes of hemoptysis. In total, 1105 adult patients were included. The etiology of hemoptysis was identified in 1042 patients (94.3%) and remained unidentified in 63 patients (5.7%). The percentage of patients with severe hypertension was significantly higher in patients with unidentified causes of hemoptysis than in those with identified causes (35% vs. 11%, p < 0.001). In multivariate analysis, age, ever-smoker, and initial systolic blood pressure were significantly associated with hemoptysis of unidentified causes. Although further studies are needed, our findings suggest a possible association between high blood pressure and cryptogenic hemoptysis.

Objective: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. Methods: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. Results: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36–0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09–1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. Conclusion: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.

Testicular Leydig cells produce testosterone through the participation of steroidogenic proteins. The CYP1B1 enzyme has been shown to catalyze 7,12-dimethylbenzanthracene (DMBA), a representative polycyclic aromatic hydrocarbon. We hypothesized that exposure to DMBA causes Leydig cell cytotoxicity through activation of CYP1B1. Leydig cells were exposed to various concentrations of DMBA for the induction of CYP1B1 expression and activity. The status of CYP1B1 function was monitored by evaluation of cytotoxicity-mediated cell death. Our data show that exposure to DMBA causes cytotoxicity in Leydig cells by CYP1B1 activation. DMBA evoked a significant increase in the generation of reactive oxygen species (ROS) by which the depolarization of mitochondrial membrane potential (MMP) is initiated and caspase-3 activation is augmented. The knockdown of CYP1B1 expression resulted in the suppression of DMBA-induced apoptosis via reduced p53 activation and caspase-3 activation, suggesting that a final metabolite of DMBA (i.e., DMBA-DE) bioactivated by CYP1B1 induces p53 activation by binding to DNA and subsequently causing apoptosis via caspase-3 activation. This finding provides evidence for constitutive expression of CYP1B1 in Leydig cells, which is a trait that only requires an initiating signal for its activity. Further research on CYP1B1 activation-provoked steroid metabolism in Leydig cells may provide decisive clues for elucidating its innate function.

OBJECTIVE Leptomeningeal metastases (LMs) in glioma have been underestimated given their low incidence and the lack of reliable imaging. Authors of this study aimed to investigate the real-world incidence of LMs using cerebrospinal fluid (CSF)–sensitive imaging, namely postcontrast fluid-attenuated inversion recovery (FLAIR) imaging, and to analyze molecular predictors for LMs in the molecular era. METHODS A total of 1405 adult glioma (World Health Organization [WHO] grade 2–4) patients underwent postcontrast FLAIR imaging at initial diagnosis and during treatment monitoring between 2001 and 2021. Collected molecular data included isocitrate dehydrogenase (IDH) mutation, 1p/19q codeletion, H3 K27 alteration, and O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation status. LM diagnosis was performed with MRI including postcontrast FLAIR sequences. Logistic regression analysis for LM development was performed with molecular, clinical, and imaging data. Overall survival (OS) was compared between patients with and those without LM. RESULTS LM was identified in 228 patients (16.2%), 110 (7.8%) at the initial diagnosis and 118 (8.4%) at recurrence. Among the molecular diagnostics, IDH-wildtype (OR 3.14, p = 0.001) and MGMT promoter unmethylation (OR 1.43, p = 0.034) were independent predictors of LM. WHO grade 4 (OR 10.52, p < 0.001) and nonlobar location (OR 1.56, p = 0.048) were associated with LM at initial diagnosis, whereas IDH-wildtype (OR 5.04, p < 0.001) and H3 K27 alteration (OR 3.39, p = 0.003) were associated with LM at recurrence. Patients with LM had a worse median OS than those without LM (16.7 vs 32.0 months, p < 0.001, log-rank test), which was confirmed as an independent factor on multivariable Cox analysis (p = 0.004). CONCLUSIONS CSF-sensitive imaging aids the diagnosis of LM, demonstrating a high incidence of LM in adult gliomas. Furthermore, molecular markers are associated with LM development in glioma, and patients with aggressive molecular markers warrant imaging surveillance for LM.

Background: Leptomeningeal metastases (LM) in glioma have been underestimated due to low incidence and lack of reliable imaging. This study aimed to investigate a real-world incidence of LM using a CSF-sensitive imaging, namely post-contrast FLAIR, and analyze molecular predictors for LM in the molecular era. Patients and Methods: Total 1,405 adult glioma patients underwent post-contrast FLAIR imaging at initial diagnosis and during treatment monitoring between 2001 and 2021. Molecular data included isocitrate dehydrogenase (IDH) mutation, 1p/19q co-deletion, H3 K27M alteration, and O6-methylguanine-methyltransferase (MGMT) promoter methylation status. LM diagnosis was performed with MRI including post-contrast FLAIR. Logistic regression analysis for LM development was performed with molecular, clinical, and imaging data. Overall survival (OS) was compared between patients with and without LM. Results: LM was identified in 228 patients (16.2%), with 110 patients (7.8%) at initial diagnosis, and 118 patients (8.4%) at recurrence. Among molecular diagnostics, IDH-wildtype (odds ratio [OR] 3.14, P = .001) and MGMT promoter unmethylation (OR=1.43, P=.034) were independent predictors of LM. WHO grade 4 (OR=10.52, P

Background: Lung epithelial cells serve as first line of defense against various inhaled pollutant particles. This study focused on assessing the impact of organic extracts of PM2.5 collected in Seoul, South Korea on primary human lung epithelial cells and identifying the relevant components and sources which induced lung epithelial cell injury.Results: We used primary lung epithelial cells isolated directly from healthy donors and evaluated the effects of organic compounds of twelve selected, seasonal PM2.5 on inflammation, cellular aging, and macroautophagy in primary lung epithelial cells. Organic extracts of PM2.5 specifically induced neutrophilic chemokine, interleukin-8, via extracellular signal regulated kinase activation. Moreover, PM2.5 significantly increased the expression of aging markers (p16, p21, and p27) and activated macroautophagy. Average mass concentrations, OC and EC, had no significant correlations with PM2.5 effects. However, regression analysis showed that polycyclic aromatic hydrocarbons and n-alkanes were the most relevant components of PM2.5 correlated with neutrophilic inflammation. Vegetative detritus and residential bituminous coal combustion sources were strongly correlated with neutrophilic inflammation, aging and macroautophagy activation.Conclusions: These data suggest that the chemical composition of PM2.5 is crucially important to determine the adverse health effects of PM2.5. Our study provides encouraging evidence to regulate the harmful components of PM2.5 in Seoul.

Poly(acrylic acid) and poly(2-(dimethylamino)ethyl acrylate) chains were grafted to polyurethane (PU) using the graft-polymerization method in order to enhance the water compatibility of PU. The grafted chains were ionized into cationic or anionic form depending on the addition of strong acid or base. The grafted polymer chains did not affect the melting, crystallization, and glass transition of the soft segment of PU due to the softness of the chain. The cross-link density and solution viscosity increased due to the linking between the grafted chains, but the slight cross-linking did not disturb the solvation of PU. The slight cross-linking notably enhanced the maximum tensile stress and shape recovery capability, and the water compatibility of PU could be notably enhanced by the grafted ionized chains. Overall, the grafting of ionized polymeric chains onto PU could enhance the hydrophilicity of PU surface, tensile strength, and shape recovery capability.

The clinical relevance of concomitant deep vein thrombosis (DVT) in patients with pulmonary embolism remains controversial. The aim of the present study was to assess clinical characteristics of patients with isolated pulmonary embolism, thereby investigating isolated pulmonary embolism related clinical factors. Patients hospitalized for pulmonary embolism who underwent DVT workup within 3 days of pulmonary embolism diagnosis were retrospectively classified into two groups: patients with isolated pulmonary embolism and patients with DVT-associated pulmonary embolism (DVT-PE). The clinical, laboratorial and radiological parameters were compared between the two groups. Of 1012 patients, 322 (31.8%) presented with isolated pulmonary embolism, and 690 (68.2%) presented with DVT-PE. In a multivariate analysis, female sex was an independent factor for predicting isolated pulmonary embolism [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.26-2.26, P < 0.001], whereas cancer (OR 0.64, 95% CI 0.43-0.96, P = 0.031), leg pain or swelling (OR 0.08, 95% CI 0.04-0.18, P < 0.001), and central pulmonary embolism (OR 0.44, 95% CI 0.32-0.59, P < 0.001) were negatively associated with isolated pulmonary embolism. There were no significant differences between the two groups with regard to risk stratification and short-term prognosis of pulmonary embolism, including adverse outcomes and pulmonary embolism related in-hospital mortality. Of pulmonary embolism patients who underwent imaging tests for DVT, approximately 32% presented with isolated pulmonary embolism. Isolated pulmonary embolism was positively associated with female sex, whereas it was negatively associated with cancer, leg pain or swelling, and central pulmonary embolism. The presence or absence of concomitant DVT did not influence the severity and short-term prognosis of pulmonary embolism.

Imaging biomarkers support the diagnosis of Alzheimer’s disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of AD spectrum. From a prospective database in an IRB-approved multicenter study (NCT02656498), 113 subjects (32 healthy control, 55 mild cognitive impairment, and 26 Alzheimer disease) with baseline structural MRI and [18F] THK-5351 PET were included. Cortical volumes were quantified from FDA-approved software for automated volumetric MRI analysis (NeuroQuant). Standardized uptake value ratio (SUVR) was calculated from tau PET images for 6 composite FreeSurfer-derived regions-of-interests approximating in vivo Braak stage (Braak ROIs). On volumetric MRI analysis, stepwise logistic regression analyses identified the cingulate isthmus and inferior parietal lobule as significant regions in discriminating AD from HC and MCI. The combined model incorporating automated volumes of selected brain regions on MRI (cingulate isthmus, inferior parietal lobule, hippocampus) and SUVRs of Braak ROIs on [18F] THK-5351 PET showed higher performance than SUVRs of Braak ROIs on [18F] THK-5351 PET in discriminating AD from HC (0.98 vs 0.88, P = 0.033) but not in discriminating AD from MCI (0.85 vs 0.79, P = 0.178). The combined model showed comparable performance to automated volumes of selected brain regions on MRI in discriminating AD from HC (0.98 vs 0.94, P = 0.094) and MCI (0.85 vs 0.78; P = 0.065).

Objective Dystrophinopathy is an X-linked recessive muscular dystrophy caused by mutations in the DMD gene. Herein we describe the prenatal detection of DMD gene mutations in a patient with no family history, by multiplex ligation-dependent probe amplification (MLPA) after noninvasive prenatal screening (NIPS). Case report A 41-year-old woman underwent NIPS owing to an advanced maternal age. A copy number variation was detected in the maternal X chromosome, and uninformative results were obtained for the fetal sex chromosomes. Following amniocentesis, a duplication was identified in exons 1–29 of the dystrophin gene by MLPA. After interviewing her family members it was confirmed that the patient is a de novo carrier of DMD duplications, and her daughter is a carrier of the same mutation. Conclusion his is the first case report to describe the prenatal diagnosis of duplications in the DMD gene by MLPA following NIPS in a patient with no family history.

Tissue conductivity measurements made with electrical properties tomography (EPT) can be used to define temporal changes in tissue habitats on longitudinal multiparametric MRI. We aimed to demonstrate the added insights for identifying tumor habitats obtained by including EPT with diffusion- and perfusion-weighted MRI, and to evaluate the use of these tumor habitats for determining tumor treatment response in post-treatment glioblastoma. Tumor habitats were developed from EPT, diffusion-weighted, and perfusion-weighted MRI in 60 patients with glioblastoma who underwent concurrent chemoradiotherapy. Voxels from EPT, apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) maps were clustered into habitats, and each habitat was serially examined to assess its temporal change. The usefulness of temporal changes in tumor habitats for diagnosing tumor progression and treatment-related change was investigated using logistic regression. The performance of significant predictors was measured using the area under the curve (AUC) from receiver-operating-characteristics analysis with 1000-fold bootstrapping. Five tumor habitats were identified, and of these, the hypervascular cellular habitat (odds ratio [OR] 5.45; 95% CI, 1.75–31.42; p = .02), hypovascular low conductivity habitat (OR 2.00; 95% CI, 1.45–3.05; p < .001), and hypovascular intermediate habitat (OR 1.57; 95% CI, 1.18–2.30; p = .006) were predictive of tumor progression. Low EPT and low CBV reflected a unique hypovascular low conductivity habitat that showed the highest diagnostic performance (AUC 0.86; 95% CI, 0.76–0.96). The combined habitats showed high performance (AUC 0.90; 95% CI, 0.82–0.98) in the differentiation of tumor progression from treatment-related change. EPT reveals low conductivity habitats that can improve the diagnosis of tumor progression in post-treatment glioblastoma. • Electrical properties tomography (EPT) demonstrated lower conductivity in tumor progression than in treatment-related change. • EPT allowed identification of a unique hypovascular low conductivity habitat when combined with cerebral blood volume mapping. • Tumor habitats with a hypovascular low conductivity habitat, hypervascular cellular habitat, and hypovascular intermediate habitat yielded high diagnostic performance for diagnosing tumor progression.

Background and Purpose: Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH. Methods: This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 µg/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups. Results: In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90±17.63 versus 30.66±32.35, P P P P Conclusions: ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study. Registration: URL: https://cris.nih.go.kr/cris/en ; Unique identifier: KCT0004628.

2,4,6-Tris(dimethylaminomethyl) phenol (TDMP) was used as a grafted functional group to modify the hydrophilicity of polyurethane (PU) and to enhance the mechanical properties and low-temperature flexibility of PU. The grafted TDMP after conversion to the ionic form notably enhanced the hydrophilicity of PU, as confirmed by the water contact angle, water swelling, and water vapor permeability results. The light crosslinking that occurred during the grafting step increased the crosslink density and solution viscosity but did not disturb the solvation of PU. The melting of the soft segment was not affected by the grafted TDMP, but the crystallization of the soft segment was significantly reduced. The breaking tensile stress and shape recovery capability were notably enhanced, but the breaking tensile strain and shape retention capability were not impaired. In addition, the grafted TDMP notably improved the flexibility of PU at very low temperature compared with that of plain PU and control series PU. Overall, it is worth grafting TDMP onto PU considering the simple preparation method, the novelty of the modification mechanism, the notable enhancement in hydrophilicity, and the potential applications in fiber and biomedical fields.

Evidence of a Wheland intermediate in carboxylate-assisted C−H activation was found using DFT calculations when the Pd(IV) catalyst species was postulated as the active catalyst species (ACS). In order to delineate the reaction mechanism of Pd-catalyzed bisarylation of 3-alkylbenzofuran, five hypothetical catalyst species, [Pd(OAc)(PMe3)(Ph)] (I), [Pd(OAc)2] (II), [Pd(OAc)2(PMe3)] (III), [Pd(OAc)2(Ph)]+ (IV) and [Pd(OAc)2(PMe3)(Ph)]+ (V) were tested as potential ACS candidates. The catalyst species I, previously reported as an ACS in the context of ambiphilic metal−ligand assistance or a concerted metalation-deprotonation mechanism, was unsuccessful, with maximum activation barriers (ΔG‡max) for the C(sp2)−H and C(sp3)−H activations of 33.3 and 51.4 kcal/mol, respectively. The ΔG‡max values for the C(sp2)−H and C(sp3)−H activations of II−V were 23.8/28.7, 32.0/49.6, 10.9/10.9, and 36.0/36.0 kcal/mol, respectively, indicating that ACS is likely IV. This catalyst species forms an intermediate state (IV_1) before proceeding to the transition state (IV_TS1,2) for C(sp2)−H activation, in which C(2) atom of 3-methylbenzofuran has a substantial σ-character. The degree of σ-character of the IV_1 state was further evaluated quantitatively in terms of geometric parameters, partial charge distribution, and activation strain analysis. The analysis results support the existence of a Wheland intermediate, which has long been recognized as the manifestation of the electrophilic aromatic substitution mechanism yet never been identified computationally.