Capturing the generation and structural transformations of molecular ions.

Molecular ions are ubiquitous and play pivotal roles1-3 in many reactions, particularly in the context of atmospheric and interstellar chemistry4-6. However, their structures and conformational transitions7,8, particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions9-11, whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even by weak nucleophiles and thus challenging to isolate or capture before they undergo further reaction. Here we show that mega-electronvolt ultrafast electron diffraction (MeV-UED)12-14, used in conjunction with resonance-enhanced multiphoton ionization, can monitor the formation of 1,3-dibromopropane (DBP) cations and their subsequent structural dynamics forming a halonium ion. We find that the DBP+ cation remains for a substantial duration of 3.6 ps in aptly named 'dark states' that are structurally indistinguishable from the DBP electronic ground state. The structural data, supported by surface-hopping simulations15 and ab initio calculations16, reveal that the cation subsequently decays to iso-DBP+, an unusual intermediate with a four-membered ring containing a loosely bound17,18 bromine atom, and eventually loses the bromine atom and forms a bromonium ion with a three-membered-ring structure19. We anticipate that the approach used here can also be applied to examine the structural dynamics of other molecular ions and thereby deepen our understanding of ion chemistry.

Use of artificial intelligence in triaging of chest radiographs to reduce radiologists' workload.

OBJECTIVES: To evaluate whether deep learning-based detection algorithms (DLD)-based triaging can reduce outpatient chest radiograph interpretation workload while maintaining noninferior sensitivity. METHODS: This retrospective study included patients who underwent initial chest radiography at the outpatient clinic between June 1 and June 30, 2017. Readers interpreted radiographs with/without a commercially available DLD that detects nine radiologic findings (atelectasis, calcification, cardiomegaly, consolidation, fibrosis, nodules, pneumothorax, pleural effusion, and pneumoperitoneum). The reading order was determined in a randomized, crossover manner. The radiographs were classified into negative and positive examinations. In a 50% worklist reduction scenario, radiographs were sorted in descending order of probability scores: the lower half was regarded as negative exams, while the remaining were read with DLD by radiologists. The primary analysis evaluated noninferiority in sensitivity between radiologists reading all radiographs and simulating a 50% worklist reduction, with the inferiority margin of 5%. The specificities were compared using McNemar's test. RESULTS: The study included 1964 patients (median age [interquartile range], 55 years [40-67 years]). The sensitivity was 82.6% (195 of 236; 95% CI: 77.5%, 87.3%) when readers interpreted all chest radiographs without DLD and 83.5% (197 of 236; 95% CI: 78.8%, 88.1%) in the 50% worklist reduction scenario. The difference in sensitivity was 0.8% (95% CI: - 3.8%, 5.5%), establishing noninferiority of 50% worklist reduction (p = 0.01). The specificity increased from 86.7% (1498 of 1728) to 90.4% (1562 of 1728) (p < 0.001) with DLD-based triage. CONCLUSION: Deep learning-based triaging may substantially reduce workload without lowering sensitivity while improving specificity. CLINICAL RELEVANCE STATEMENT: Substantial workload reduction without lowering sensitivity was feasible using deep learning-based triaging of outpatient chest radiograph; however, the legal responsibility for incorrect diagnoses based on AI-standalone interpretation remains an issue that should be defined before clinical implementation. KEY POINTS: • A 50% workload reduction simulation using deep learning-based detection algorithm maintained noninferior sensitivity while improving specificity. • The CT recommendation rate significantly decreased in the disease-negative patients, whereas it slightly increased in the disease-positive group without statistical significance. • In the exploratory analysis, the noninferiority of sensitivity was maintained until 70% of the workload was reduced; the difference in sensitivity was 0%.

Feasibility and usefulness of cognitive monitoring using a new home-based cognitive test in mild cognitive impairment: a prospective single arm study.

BACKGROUND: The risk of dementia is increased in subjects with mild cognitive impairment (MCI). Despite the plethora of in-person cognitive tests, those that can be administered over the phone are lacking. We hypothesized that a home-based cognitive test (HCT) using phone calls would be feasible and useful in non-demented elderly. We aimed to assess feasibility and validity of a new HCT as an optional cognitive monitoring tool without visiting hospitals. METHODS: Our study was conducted in a prospective design during 24 weeks. We developed a new HCT consisting of 20 questions (score range 0-30). Participants with MCI (n = 38) were consecutively enrolled and underwent regular HCTs during 24 weeks. Associations between HCT scores and in-person cognitive scores and Alzheimer's disease (AD) biomarkers were evaluated. In addition, HCT scores in MCI participants were cross-sectionally compared with age-matched cognitively normal (n = 30) and mild AD dementia (n = 17) participants for discriminative ability of the HCT. RESULTS: HCT had good intra-class reliability (test-retest Cronbach's alpha 0.839). HCT scores were correlated with the Mini-Mental State Examination (MMSE), verbal memory delayed recall, and Stroop test scores but not associated with AD biomarkers. HCT scores significantly differed among cognitively normal, MCI, and mild dementia participants, indicating its discriminative ability. Finally, 32 MCI participants completed follow-up evaluations, and 8 progressed to dementia. Baseline HCT scores in dementia progressors were lower than those in non-progressors (p = 0.001). CONCLUSION: The feasibility and usefulness of the HCT were demonstrated in elderly subjects with MCI. HCT could be an alternative option to monitor cognitive decline in early stages without dementia.

Cerium Photocatalyst in Action: Structural Dynamics in the Presence of Substrate Visualized via Time-Resolved X-ray Liquidography.

[Ce(III)Cl6]3-, with its earth-abundant metal element, is a promising photocatalyst facilitating carbon-halogen bond activation. Still, the structure of the reaction intermediate has yet to be explored. Here, we applied time-resolved X-ray liquidography (TRXL), which allows for direct observation of the structural details of reaction intermediates, to investigate the photocatalytic reaction of [Ce(III)Cl6]3-. Structural analysis of the TRXL data revealed that the excited state of [Ce(III)Cl6]3- has Ce-Cl bonds that are shorter than those of the ground state and that the Ce-Cl bond further contracts upon oxidation. In addition, this study represents the first application of TRXL to both photocatalyst-only and photocatalyst-and-substrate samples, providing insights into the substrate's influence on the photocatalyst's reaction dynamics. This study demonstrates the capability of TRXL in elucidating the reaction dynamics of photocatalysts under various conditions and highlights the importance of experimental determination of the structures of reaction intermediates to advance our understanding of photocatalytic mechanisms.

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.

Association of main meal frequency and skipping with metabolic syndrome in Korean adults: a cross-sectional study.

BACKGROUND: Reduced meal frequency can increase the risk of metabolic syndrome (MetS). However, limited studies have examined the association between meal frequency and skipping meals with MetS. This study aims to analyze the association between main meal frequency and meal skipping with MetS in Korean adults aged ≥ 19 years. METHODS: In this study, we included data from 22,699 Korean adult participants from the 2016-2020 Korea National Health and Nutrition Examination Survey (KNHANES). The 24-h dietary recall method was used to classify the participants into three groups based on main meal frequency (one, two, or three meals per day) and seven groups based on the type of main meal they skipped. Multivariable logistic regression analysis was conducted to determine the association between main meal frequency and the types of main meals skipped with the odds of MetS and its associated components. Appropriate estimates were accounted for using sampling weights, stratification, and clustering. RESULTS: The prevalence of MetS in the study population was 33.8%. The average age of the participants was 47.2 years with 42.6% being men, and 57.4% being women. Men who consumed two meals per day had higher odds of MetS than those who consumed three meals per day (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.01-1.33). Women who consumed two meals per day, and skipped breakfast had increased odds of having elevated fasting blood glucose levels (OR 1.18, 95% CI 1.02-1.35), and elevated triglycerides (OR 1.19, 95% CI 1.02-1.39). However, women who skipped dinner had reduced odds of having elevated fasting blood glucose levels (OR 0.74, 95% CI 0.58-0.94). CONCLUSIONS: Our findings suggest that meal frequency and the type of main meal skipped may be associated with MetS and emphasize the importance of consuming breakfast to prevent MetS.

Interactions between Bitter Taste Receptor Gene Variants and Dietary Intake Are Associated with the Incidence of Type 2 Diabetes Mellitus in Middle-Aged and Older Korean Adults.

The relationship between the variants of bitter taste receptor gene TAS2R4, dietary intake, and incidence of type 2 diabetes mellitus (T2DM) remains unclear. Hence, we aimed to examine the association of TAS2R4 rs2233998 variants with T2DM incidence in middle-aged and older Korean adults to understand if their association was modulated by dietary intake. Data of the Ansan-Ansung cohort from the Korean Genome and Epidemiology Study were used in this study. A total of 4552 Korean adults aged 40-69 years with no history of T2DM or cancer at baseline were followed-up for 16 years. Dietary intake was assessed using a 103-item food frequency questionnaire, and new T2DM cases were defined based on the World Health Organization and International Diabetes Federation criteria. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM incidence. During the mean follow-up period of 11.97 years, 1082 (23.77%) new T2DM cases were identified. Women carrying the TT genotype of TAS2R4 rs2233998 exhibited 1.48 times higher incidence of T2DM (HR: 1.48; 95 CI: 1.13-1.93) than those carrying the CC genotype. TAS2R4 rs2233998 variants were positively associated with the incidence of T2DM among Korean women with high intakes of carbohydrates or sugars and low intakes of fruits or vegetables. TT carrier women in the highest tertile of carbohydrate or sugar intake exhibited an increased incidence of T2DM (HR: 2.08, 95% CI: 1.33-3.27 for carbohydrates; HR: 2.31, 95% CI: 1.53-3.51 for sugars) than CC carrier women. Women carrying the TT genotype in the lowest tertile exhibited an increased incidence of T2DM (HR: 1.55, 95% CI: 1.02-2.37 for vegetables; HR: 1.62, 95% CI: 1.06-2.48 for fruits) than women carrying the CC genotype in the highest tertile of vegetable or fruit consumption. However, no association was observed between TAS2R4 rs2233998 variants and dietary intake with T2DM incidence in Korean men. Our findings suggest that variants of TAS2R4 rs2233998 are associated with T2DM incidence, and their associations are strengthened by excessive intake of carbohydrates or sugars and inadequate intake of fruits or vegetables. Diet encompassing optimal intake of carbohydrates or sugars and high intake of fruits or vegetables may minimize the risk of developing T2DM.

Trends in intake and sources of dietary protein in Korean adults, 1998-2018.

Although a decrease in carbohydrate intake and an increase in fat intake among Koreans have been reported, investigations of changes in protein intake have been limited. Thus, this study aimed to explore trends in the dietary intake of total, plant and animal proteins overall and by socio-demographic subgroups in Korea over the past two decades. A total of 78 716 Korean adults aged ≥ 19 years who participated in the seven survey cycles of the Korea National Health and Nutrition Examination Survey 1998-2018 were included. Dietary protein intake, overall and by source, was calculated using a single 24-h dietary recall data. Changes in dietary protein over 20 years were estimated using multiple linear regression analysis after adjusting for potential covariates. For total protein intake, a significant decrease was reported from 1998 to 2016-2018 (P for trendlinearity < 0·001), whereas an increasing trend was observed from 2007-2009 to 2016-2018 (P for trendlinearity < 0·001). In terms of protein intake by source, plant protein intake decreased while animal protein intake increased over the past two decades, indicating steeper trends during the recent decade (P for trendlinearity < 0·001). These trends were more pronounced among younger adults and those with higher household income and education levels. These findings suggest that continuous monitoring of dietary protein intake overall and by source (plant v. animal) across socio-demographic group is needed.

Retroreflection-based sandwich type affinity sensing of isothermal gene amplification products for foodborne pathogen detection.

Loop-mediated isothermal amplification (LAMP) is an outstanding method for molecular diagnostics, as the rapid, specific, and sensitive amplification of target genes is possible. However, it is necessary to measure fluorescence in the quantitative analysis of LAMP products, so a sophisticated optical setup is required. This study tried to develop a novel sensing method that can quantify target analytes with simple equipment, such as nonspectroscopic white light and a CMOS camera. To achieve this, a retroreflective Janus particle (RJP) as a probe and specially designed loop primers, fluorescein isothiocyanate (FITC)- and biotin-modified loop primers, were introduced into the LAMP system. By performing LAMP in the presence of designed primers, double-stranded amplicons possessing FITC and biotin labels at each end are generated in proportion to the quantity of the target pathogen. Using the anti-FITC antibody-modified sensing surface and streptavidin-conjugated RJP probes, the amplicons can be captured in sandwich-configuration and detected under nonspectroscopic conditions composed of white light and a camera. To confirm the feasibility of the sensing system, the invA gene of Salmonella was selected as the target. It was possible to quantitatively analyze the Salmonella concentration from 0 to 106 colony-forming units, sufficiently covering the required detection range. In addition, quantitative analyses of pathogens in contaminated food sources, including milk and chicken meat, were successfully conducted with a limit of detection of 10 CFU.

Pro-inflammatory diet associated with low back pain in adults aged 50 and older.

AIMS: To investigate the association between pro-inflammatory diets and low back pain in a nationally representative sample of Korean adults. BACKGROUND: Low back pain is one of the most common health issues. Evidence suggests a potential association between systemic inflammation and the development of low back pain, and the role of diet in mitigating the inflammation that, in turn, can alleviate low back pain. METHODS: This cross-sectional, correlational study used data from the 6th Korea National Health and Nutrition Examination Survey involving health interviews, examinations, and nutritional surveys. Dietary inflammatory index scores were generated based on 24-hour dietary recalls. Respondents were asked if they had experienced low back pain for at least 30 days in the past three months. Multiple logistic regression analyses were conducted to investigate the independent association between pro-inflammatory diets and low back pain. RESULTS: Of 7346 respondents, most participants were middle-aged, married, and non-/ex-smokers, lived in 2+ person households, consumed alcohol less than once a week, and had no allergies or underlying medical conditions. Respondents in the highest inflammatory diet quintile had nearly 0.25 higher odds of reporting low back pain than those in the lowest quintile (adjusted ORquintile5vs1: 1.25, 95%CI [1.01-1.54]; p = .043). CONCLUSIONS: Results from this study indicate a role of pro-inflammatory diets in the development of low back pain. Nurses can screen for those consuming pro-inflammatory foods, and thus, are vulnerable to back pain, and aid in the delivery of tailored nutritional education. Future studies should investigate how diet affects low back pain diagnosis and chronicity relative to pain phenotypes.

Lung cancer probability and clinical outcomes of baseline and new subsolid nodules detected on low-dose CT screening.

BACKGROUND: Limited data are available regarding the management of subsolid nodules detected on lung cancer screening with low-dose CT (LDCT). We aimed to determine the characteristics of screen-detected subsolid nodules, and to evaluate the probability of lung cancer and the clinical course of subsolid nodules detected at baseline and during follow-up screening. METHODS: We evaluated 50 132 asymptomatic adults (22 631 never-smokers and 27 501 ever-smokers) who underwent LDCT screening for lung cancer between May 2003 and June 2019 at a tertiary centre in South Korea. The incidence, characteristics and clinical outcomes of the baseline and new screen-detected subsolid nodules were determined. RESULTS: A total of 6725 subsolid nodules (5116 pure ground glass opacity nodules and 1609 part-solid nodules) were detected in 4545 participants (1484 new subsolid nodules detected in 937 (1.9%) participants; the overall incidence of subsolid nodules: 10.7% in never-smokers and 7.7% in ever-smokers, p<0.001). Among 4918 subsolid nodules that underwent follow-up with CT scans (the mean number of CT scans, including the baseline LDCT scan: 4.6), 2116 nodules (30.0% of baseline subsolid nodules and 78.9% of new subsolid nodules) resolved spontaneously. Among 293 biopsied subsolid nodules, 227 (77.5%) nodules were diagnosed as lung cancer, of which 226 (99.6%) were adenocarcinomas. No significant difference was observed in pathological invasiveness or the initial stage between the baseline and new cancerous subsolid nodules. Multivariable analyses revealed that new detection at follow-up screening was significantly associated with a lower probability of lung cancer (OR 0.26, 95% CI 0.14 to 0.49) and overall growth (OR 0.39, 95% CI 0.26 to 0.59), but with a higher probability of resolution (OR 6.30, 95% CI 5.09 to 7.81). CONCLUSIONS: LDCT screening led to a considerably high rate of subsolid nodule detection, particularly in never-smokers. Compared with the baseline subsolid nodules, the new subsolid nodules were associated with a lower probability of lung cancer and higher probability of spontaneous resolution, indicating their more inflammatory nature. Less aggressive follow-up may be allowed for new subsolid nodules, particularly in screening programmes for Asian populations.

Interobserver variability in Lung CT Screening Reporting and Data System categorisation in subsolid nodule-enriched lung cancer screening CTs.

OBJECTIVES: To assess interobserver agreement in Lung CT Screening Reporting and Data System (Lung-RADS) categorisation in subsolid nodule-enriched low-dose screening CTs. METHODS: A retrospective review of low-dose screening CT reports from 2013 to 2017 using keyword searches for subsolid nodules identified 54 baseline CT scans. With an additional 108 negative screening CT scans, a total of 162 CT scans were categorised according to the Lung-RADS by two fellowship-trained thoracic radiologists in consensus. We randomly selected 20, 20, 10, and 10 scans from categories 1/2, 3, 4A, and 4B CT scans, respectively, to ensure balanced category representation. Five radiologists classified the 60 CT scans into Lung-RADS categories. The frequencies of concordance and minor and major discordance were calculated, with major discordance defined as at least 6 months of management discrepancy. We used Cohen's κ statistics to analyse reader agreement. RESULTS: An average of 60.3% (181 of 300) of all cases and 45.0% (90 of 200) of positive screens were correctly categorised. The minor and major discordance rates were 12.3% and 27.3% overall and 18.5% and 36.5% in positive screens, respectively. The concordance rate was significantly higher among experienced thoracic radiologists. Overall, the interobserver agreement was moderate (mean κ, 0.45; 95% confidence interval: 0.40-0.51). The proportion of part-solid risk-dominant nodules was significantly higher in cases with low rates of accurate categorisation. CONCLUSION: This retrospective study observed variable accuracy and moderate interobserver agreement in radiologist categorisation of subsolid nodules in screening CTs. This inconsistency may affect management recommendations for lung cancer screening. KEY POINTS: • Diagnostic performance for Lung-RADS categorisation is variable among radiologists with fair to moderate interobserver agreement in subsolid nodule-enriched CT scans. • Experienced thoracic radiologists showed more accurate and consistent Lung-RADS categorisation than radiology residents. • The relative abundance of part-solid nodules was a potential factor related to increased disagreement in Lung-RADS categorisation.

Deep Learning-based Automatic Detection Algorithm for Reducing Overlooked Lung Cancers on Chest Radiographs.

Background It is uncertain whether a deep learning-based automatic detection algorithm (DLAD) for identifying malignant nodules on chest radiographs will help diagnose lung cancers. Purpose To evaluate the efficacy of using a DLAD in observer performance for the detection of lung cancers on chest radiographs. Materials and Methods Among patients diagnosed with lung cancers between January 2010 and December 2014, 117 patients (median age, 69 years; interquartile range [IQR], 64-74 years; 57 women) were retrospectively identified in whom lung cancers were visible on previous chest radiographs. For the healthy control group, 234 patients (median age, 58 years; IQR, 48-68 years; 123 women) with normal chest radiographs were randomly selected. Nine observers reviewed each chest radiograph, with and without a DLAD. They detected potential lung cancers and determined whether they would recommend chest CT for follow-up. Observer performance was compared with use of the area under the alternative free-response receiver operating characteristic curve (AUC), sensitivity, and rates of chest CT recommendation. Results In total, 105 of the 117 patients had lung cancers that were overlooked on their original radiographs. The average AUC for all observers significantly rose from 0.67 (95% confidence interval [CI]: 0.62, 0.72) without a DLAD to 0.76 (95% CI: 0.71, 0.81) with a DLAD (P < .001). With a DLAD, observers detected more overlooked lung cancers (average sensitivity, 53% [56 of 105 patients] with a DLAD vs 40% [42 of 105 patients] without a DLAD) (P < .001) and recommended chest CT for more patients (62% [66 of 105 patients] with a DLAD vs 47% [49 of 105 patients] without a DLAD) (P < .001). In the healthy control group, no difference existed in the rate of chest CT recommendation (10% [23 of 234 patients] without a DLAD and 8% [20 of 234 patients] with a DLAD) (P = .13). Conclusion Using a deep learning-based automatic detection algorithm may help observers reduce the number of overlooked lung cancers on chest radiographs, without a proportional increase in the number of follow-up chest CT examinations. © RSNA, 2020 Online supplemental material is available for this article.

Low-dose chest computed tomographic screening and invasive diagnosis of pulmonary nodules for lung cancer in never-smokers.

BACKGROUND: Although lung cancer screening using low-dose computed tomography (LDCT) is now widely used in clinical practice, the characteristics and outcomes of diagnostic procedures related to screen-detected nodules in never-smokers remain unclear. We aimed to determine the incidence of nodules considered for invasive biopsy and evaluate the final diagnoses and procedure-related complications in never-smokers in comparison to ever-smokers who underwent LDCT screening. METHODS: We evaluated 37 436 asymptomatic adults (17 968 never-smokers and 19 468 ever-smokers) who underwent LDCT screening for lung cancer between January 2009 and December 2018 at a tertiary centre in South Korea. The rates of invasive diagnostic procedures for detected nodules and related complications, and the diagnostic outcomes were determined in the never-smoker and ever-smoker groups. RESULTS: Among the never-smokers, 2908 (16.2%) out of 17 968 had positive nodules. Overall, 139 (0.77%) out of 17 968 never-smokers and 194 (1.00%) out of 19 468 ever-smokers underwent invasive biopsy (p=0.022). Lung cancer was diagnosed in 84 (0.47%) out of 17 968 never-smokers and 123 (0.63%) out of 19 468 ever-smokers (p=0.032). The proportions of participants diagnosed with benign disease after invasive biopsy (false-positive) were 50 (0.28%) out of 17 968 and 69 (0.35%) out of 19 468 in the never-smoker and ever-smoker groups, respectively (p=0.191). Multivariate analyses revealed no significant associations of smoking with the risk of a false-positive diagnosis (OR 0.98, 95% CI 0.62-1.57) and complications (OR 1.33, 95% CI 0.65-3.73) after biopsy. Of the 84 never-smokers with lung cancer, 82 (97.6%) had adenocarcinoma, and 75 (89.3%) were in stage I with a favourable prognosis. CONCLUSIONS: LDCT screening in never-smokers resulted in a notable detection rate of lung nodules, which warranted invasive biopsy. The lung cancer detection rate was lower in never-smokers than in ever-smokers. However, no significant differences in the false-positive and complication rates were observed between the two groups. Accordingly, a more specifically tailored management strategy is needed for screen-detected nodules in Asian never-smokers.

Correction to: Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

In the original article there are errors in Fig. 3. Following is the corrected figure.

Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

OBJECTIVES: Subsolid lung adenocarcinoma with cystic airspaces (LACA) is a unique manifestation of lung cancer. This study was conducted to establish a radiologic disease progression model of LACA and to explore its association with the clinical course and clinicopathologic features of LACA. MATERIALS AND METHODS: Sixty patients with LACA who underwent surgery at our center between 2004 and 2017 were retrospectively reviewed. The morphological changes of LACA over time on 98 serial computed tomography scans from 27 of 60 patients were tracked to establish a radiologic disease progression model. Associations between this model and the clinicopathologic characteristics of LACA were investigated. RESULTS: The following stepwise progression model of LACA was developed: in phase I, cystic airspaces (CAs) appear in the middle of non-solid nodules; in phase II, the CAs grow; in phase III, a solid component appears on the border of the CAs; and in phase IV, the solid component gradually surrounds the CAs and becomes thicker, and the CAs shrink. In total, 10 (17%), 33 (55%), and 17 (28%) LACA patients were classified as belonging to phases II, III, and IV at the time of surgery, respectively. More advanced phases were associated with higher pathologic T and N staging, lymphovascular invasion, visceral pleural invasion, spread through air spaces, and solid/micropapillary subtype. In the multivariate analysis, our model demonstrated a good discrimination capability for cancer recurrence risk. CONCLUSIONS: The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.

Novel lineage 1 recombinants of porcine reproductive and respiratory syndrome virus isolated from vaccinated herds: genome sequences and cytokine production profiles.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a widely disseminated, macrophage-tropic arterivirus that exhibits profound genetic and pathogenic heterogeneity. The present study was conducted to determine the complete genome sequences of two novel Korean lineage 1 PRRSV-2 strains, KNU-1901 and KNU-1902, which were isolated from vaccinated pig farms experiencing unusually high morbidity and mortality. Both isolates contained notable discontinuous 423-nucleotide deletions (DELs) within the genes encoding nonstructural protein 2 (nsp2) and GP3 when compared with the prototype strain VR-2332. In particular, the nsp2 DEL viruses had unique quadripartite discontinuous DEL signatures (111-1-19-9) in nsp2; this is an expanded version of the tripartite 111-1-19 DEL previously identified in virulent lineage 1 PRRSV-2 strains. Phylogenetic analysis revealed that both novel nsp2 DEL viruses belong to the Korean clade (KOR C) of lineage 1 isolates based on ORF5 but cluster with lineage KOR A strains based on the nsp2 or complete genome sequence. Recombination detection analysis suggested that both novel isolates are recombinants and may have evolved via natural inter-lineage recombination between circulating KOR A and KOR C strains. Interestingly, compared with the prototype VR-2332 virus, the novel nsp2 DEL variants were less efficient at promoting the expression of immune response genes in porcine alveolar macrophage culture. Taken together, we conclude that KNU-1901 and KNU-1902 are recently evolved recombinant variants of the virulent lineage 1 family that caused the regional severe PRRS outbreaks.

Positive association between dietary acid load and future insulin resistance risk: findings from the Korean Genome and Epidemiology Study.

BACKGROUND: Acid-base homeostasis is increasingly being recognized to play an important role in normal metabolic function. However, prospective studies on the relationship between diet-induced acid-base imbalance and insulin resistance among Asian populations have been limited. Thus, we investigated whether diet-induced metabolic acidosis was prospectively associated with insulin resistance risk in middle-aged and older Korean adults. METHODS: In total, 5406 participants from the Korean Genome and Epidemiology Study without type 2 diabetes, insulin resistance, cancer, or renal diseases at baseline examination were included in this study. To estimate diet-induced metabolic acidosis, we used potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores calculated from the usual dietary intake assessed by a validated 103-item food frequency questionnaire at baseline. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of insulin resistance incidence. RESULTS: During a mean follow-up period of 7.4 years, we documented 3449 insulin resistance cases. In the fully adjusted model, the future insulin resistance risk was significantly higher among participants in the highest quartiles of PRAL (HR: 1.30, 95% CI: 1.13-1.48, Ptrend = 0.0002) and NEAP (HR: 1.30, 95% CI: 1.14-1.49, Ptrend = 0.0008) than among those in the lowest quartiles. Associations were slightly strengthened among men, adults < 50 years old, obese participants, or those with low physical activity levels. CONCLUSIONS: Our findings suggested that diet-dependent acid load was positively associated with the future development of insulin resistance, suggesting effect modification by sex, age, the presence of obesity, and physical activity levels.

Association Between Post-Resuscitation Coronary Angiography With and Without Intervention and Neurological Outcomes After Out-of-Hospital Cardiac Arrest.

Objective: This study aimed to investigate the association between coronary angiography (CAG) with and without percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest (OHCA) and neurological recovery and to determine the influence of primary electrocardiogram or patient age on the effects of CAG. Methods: Adult patients with OHCA with cardiac etiology who were admitted to PCI-capable hospitals from 2016 to 2017 were enrolled in this study from the nationwide OHCA registry of Korea. Coronary intervention was categorized into three groups: No CAG, CAG without PCI, and CAG with PCI. The endpoint was good neurological recovery. Multivariable logistic regression and interaction analyses (intervention × electrocardiogram and intervention × age) were conducted by calculating adjusted odds ratios (aORs) and 95% confidence intervals (CI). Results: Of a total of 6,802 eligible OHCA patients, 1,218 (17.9%) underwent CAG without PCI and 1,136 (16.7%) underwent CAG with PCI. The CAG without PCI and CAG with PCI groups were more likely to have good neurological recovery than the No CAG group (57.4% vs. 61.6% vs. 16.3%; 3.39 [2.83-4.06] for CAG without PCI and 3.32 [2.74-4.01] for CAG with PCI). Interaction analysis showed that although the effect size differed according to patient characteristics, both CAG groups were associated with an increased likelihood of good neurological recovery, regardless of primary electrocardiogram and age group. In younger patients, CAG with PCI had greater outcome benefits than CAG without PCI (8.54 [4.31-16.95] vs. 4.10 [2.69-6.24]), whereas CAG without PCI had a larger effect size than CAG with PCI in elderly patients (4.46 [2.59-7.68] vs. 2.92 [1.80-4.73]) (p value for interaction 0.02). Conclusions: Post-resuscitation CAG with and without PCI are associated with better neurological recovery in patients with OHCA, regardless of primary electrocardiogram and patient age.

Administration of encapsulated L-tryptophan improves duodenal starch digestion and increases gastrointestinal hormones secretions in beef cattle.

OBJECTIVE: This study investigated the effects of oral administration of rumen-protected L-tryptophan (RPL-T) on duodenal starch digestion and gastrointestinal hormones (GIH) secretions using Hanwoo beef steers as the animal models. METHODS: Four steers (423±24 kg) fitted with ruminal and duodenal cannulas were employed in a crossover design replicated twice. Treatments were control (basal diet) and RPL-T (basal diet+191.1 mg/kg body weight [BW]) group. Blood and duodenal samples were collected to measure serum GIH levels and pancreatic α-amylase activity at day 0, 1, 3, and 5 (-30, 30, 90, 150, and 210 min) of the study. Samples from each segment of the gastrointestinal tract were collected via ruminal and duodenal cannulas and were used to determine soluble protein and the starch digestion rate at days 6 (-30, 180, 360, and 540 min) and 8 (-30, 90, 270, and 450 min) of the experiment. RESULTS: No significant difference in ruminal pH, NH3-N, and total volatile fatty acid including the levels of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, and the acetate-to-propionate ratio was observed between groups (p>0.05). Crude protein uptake was higher and feces starch content was lower in RPL-T group than the control group (p<0.05). The D-glucose contents of feces in RPL-T group decreased at day 5 compared to those in the control group (p<0.05), however, no change was found at day 0, 1, or 3 compared to the control group (p>0.05). Serum cholecystokinin (CCK), melatonin, duodenal pancreatic α-amylase activity, and starch digestion were significantly higher in RPL-T group than the control group (p<0.05). CONCLUSION: Taken together, oral administration of RPL-T at the rate of 191.1 mg/kg BW consistently increased CCK concentration, pancreatic α-amylase activity in duodenal fluids, and starch digestion rate in the small intestine and thus found to be beneficial.