DNA-PKcs-PIDDosome: a nuclear caspase-2-activating complex with role in G2/M checkpoint maintenance.

Caspase-2 is unique among all the mammalian caspases in that it is the only caspase that is present constitutively in the cell nucleus, in addition to other cellular compartments. However, the functional significance of this nuclear localization is unknown. Here we show that DNA damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the S122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase DNA-PKcs and promoted by the p53-inducible death-domain-containing protein PIDD within a large nuclear protein complex consisting of DNA-PKcs, PIDD, and caspase-2, which we have named the DNA-PKcs-PIDDosome. This phosphorylation and the catalytic activity of caspase-2 are involved in the maintenance of a G2/M DNA damage checkpoint and DNA repair mediated by the nonhomologous end-joining (NHEJ) pathway. The DNA-PKcs-PIDDosome thus represents a protein complex that impacts mammalian G2/M DNA damage checkpoint and NHEJ.

Association Between Commuting Time and Subjective Well-Being in Relation to Regional Differences in Korea.

BACKGROUND: Long commuting times have a negative impact on mental health. However, few studies have explored the relationship between commuting time and well-being based on urbanization by region. Our study examines this relationship as well as the effect of regional differences on Korean workers. METHODS: We used data from the sixth Korean Working Conditions Survey. Commuting time and occupational factors were assessed using a questionnaire, and subjective well-being was assessed using the World Health Organization-5 Well-Being Index. Regions were divided into the cities and the provinces based on Korea's administrative divisions. Logistic regression analysis was performed to investigate the association between commuting time and well-being. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for well-being were estimated, using participants commuting time of < 20 minutes as a reference group. RESULTS: The total number of workers was 29,458 (13,855 men, 15,603 women). We found higher aORs for low well-being among workers with long commuting times (aOR, 1.23; 95% CI, 1.11-1.36 and aOR, 1.28; 95% CI, 1.16-1.42 for 60-79 and ≥ 80 minutes, respectively). When stratified by sex and region, higher aORs for low well-being were found only in the workers who lived in cities. CONCLUSION: Long commuting time was negatively associated with well-being in Korean wage workers living in the cities. Policies for reducing commuting time should be discussed to address the mental health of workers, especially those living in metropolitan cities.

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

Mortality and lung function decline in patients who develop chronic pulmonary aspergillosis after lung cancer surgery.

BACKGROUND: Lung cancer surgery is reported as a risk factor for chronic pulmonary aspergillosis (CPA). However, limited data are available on its clinical impact. We aimed to determine the effect of developed CPA after lung cancer surgery on mortality and lung function decline. METHODS: We retrospectively identified the development of CPA after lung cancer surgery between 2010 and 2016. The effect of CPA on mortality was evaluated using multivariable Cox proportional hazard analyses. The effect of CPA on lung function decline was evaluated using multiple linear regression analyses. RESULTS: During a median follow-up duration of 5.01 (IQR, 3.41-6.70) years in 6777 patients, 93 developed CPA at a median of 3.01 (IQR, 1.60-4.64) years. The development of CPA did not affect mortality in multivariable analysis. However, the decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were greater in patients with CPA than in those without (FVC, - 71.0 [- 272.9 to - 19.4] vs. - 10.9 [- 82.6 to 57.9] mL/year, p < 0.001; FEV1, - 52.9 [- 192.2 to 3.9] vs. - 20.0 [- 72.6 to 28.6] mL/year, p = 0.010). After adjusting for confounding factors, patients with CPA had greater FVC decline (ß coefficient, - 103.6; 95% CI - 179.2 to - 27.9; p = 0.007) than those without CPA. However, the FEV1 decline (ß coefficient, - 14.4; 95% CI - 72.1 to 43.4; p = 0.626) was not significantly different. CONCLUSION: Although the development of CPA after lung cancer surgery did not increase mortality, the impact on restrictive lung function deterioration was profound.

Pleural recurrence after transthoracic needle lung biopsy in stage I lung cancer: a systematic review and individual patient-level meta-analysis.

INTRODUCTION: Conflicting results exist regarding whether preoperative transthoracic biopsy increases the risk of pleural recurrence in early lung cancer. We conducted a systematic, patient-level meta-analysis to evaluate the risk of pleural recurrence in stage I lung cancer after percutaneous transthoracic lung biopsy. METHODS: A systematic search of OVID-MEDLINE, Embase and the Cochrane Database of Systematic Reviews was performed through October 2018. Eligible studies were original articles on the risk of pleural recurrence in stage I lung cancer after transthoracic biopsy. We contacted the corresponding authors of eligible studies to obtain individual patient-level data. We used the Fine-Gray model for time to recurrence and lung cancer-specific survival and a Cox proportional hazards model for overall survival. RESULTS: We analysed 2394 individual patient data from 6 out of 10 eligible studies. Compared with other diagnostic procedures, transthoracic biopsy was associated with a higher risk for ipsilateral pleural recurrence, which manifested solely (subdistribution HR (sHR), 2.58; 95% CI 1.15 to 5.78) and concomitantly with other metastases (sHR 1.99; 95% CI 1.14 to 3.48). In the analysis of secondary outcomes considering a significant interaction between diagnostic procedures and age groups, reductions of time to recurrence (sHR, 2.01; 95% CI 1.11 to 3.64), lung cancer-specific survival (sHR 2.53; 95% CI 1.06 to 6.05) and overall survival (HR 2.08; 95% CI 1.12 to 3.87) were observed in patients younger than 55 years, whereas such associations were not observed in other age groups. DISCUSSION: Preoperative transthoracic lung biopsy was associated with increased pleural recurrence in stage I lung cancer and reduced survival in patients younger than 55 years.

Effects of Antithrombotic Treatment on Bleeding Complications of EBUS-TBNA.

Background and Objectives: The application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been markedly increased over the past decade. EBUS-TBNA is known to be a very safe and accurate procedure; however, the incidence of bleeding complications in patients who are taking antithrombotic agents (ATAs) is not well established. Materials and Methods: We conducted a retrospective analysis of a prospectively registered EBUS-TBNA cohort in a single tertiary hospital from May 2009 to December 2016. The patients were divided into two groups: an insufficient discontinuation group, defined as having a prescription for ATAs on the procedure day or only interrupting them for a short period of time, and a sufficient discontinuation group, defined as having prescription for ATAs during 30 days prior to the procedure and interrupting them for a sufficient period of time. Results: During the study period, a total of 4271 patients, after excluding 3773 patients who did not take ATAs at all, 498 patients were classified into the insufficient discontinuation group (n = 102) and the sufficient discontinuation group (n = 396). The baseline characteristics of patients and examined lesions between two groups were not significantly different, except insufficient discontinuation group had longer prothrombin times than the sufficient discontinuation group. In the insufficient discontinuation group, the most common reasons for prescriptions of ATAs were ischemic heart disease (48.0%) and cerebral vascular disease (28.4%), and half of the patients were taking two or more ATAs. Eventually, only one bleeding complication in the insufficient discontinuation group (1/102, 1.0%) and one event in the sufficient discontinuation group (1/396, 0.3%) occurred (p = 0.368). Conclusions: EBUS-TBNA is considered a safe procedure in terms of bleeding complications, even in patients with insufficient stopping of ATAs.

Which definition of a central tumour is more predictive of occult mediastinal metastasis in nonsmall cell lung cancer patients with radiological N0 disease?

BACKGROUND: Guidelines recommend invasive mediastinal staging for centrally located tumours, even in radiological N0 nonsmall cell lung cancer (NSCLC). However, there is no uniform definition of a central tumour that is more predictive of occult mediastinal metastasis. METHODS: A total of 1337 consecutive patients with radiological N0 disease underwent invasive mediastinal staging. Tumours were categorised into central and peripheral by seven different definitions. RESULTS: About 7% (93 out of 1337) of patients had occult N2 disease, and they had significantly larger tumour size and more solid tumours on computed tomography. After adjustment for patient- and tumour-related characteristics, only the central tumour definition of the inner one-third of the hemithorax adopted by drawing concentric lines arising from the midline significantly predicted occult N2 disease (adjusted OR 2.13, 95% CI 1.17-3.87; p=0.013). This association was maintained after excluding patients with pure ground-glass nodules (adjusted OR 2.54, 95% CI 1.37-4.71; p=0.003) or only including those with solid tumours (adjusted OR 2.30, 95% CI 1.08-4.88; p=0.030). CONCLUSIONS: We suggest that a central tumour should be defined using the inner one-third of the hemithorax adopted by drawing concentric lines from the midline. This is particularly useful for predicting occult N2 disease in patients with NSCLC.

Clinical usefulness of routine AFB culture and MTB PCR of EBUS-TBNA needle rinse fluid.

BACKGROUND AND OBJECTIVE: We evaluated the usefulness of acid-fast bacilli (AFB) culture and Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid for diagnosing tuberculous lymphadenitis. METHODS: EBUS-TBNA needle rinse fluid was routinely used for AFB culture and MTB PCR. The patients were categorized according to the pre-procedural diagnosis (Group A, suspected/histology-confirmed lung cancer; Group B, extrapulmonary malignancy; and Group C, other benign diseases). RESULTS: Of the 4672 subjects, 104 (2.2%) were diagnosed with tuberculous lymphadenitis; 1.0%, 4.6% and 12.7% of Group A, B and C, respectively. Tuberculous lymphadenitis was diagnosed in 0.2%, 1.0% and 4.5% Group A, B and C patients, respectively, by histopathology. On addition of AFB culture to histopathology, tuberculous lymphadenitis was diagnosed in 1.0%, 4.4% and 10.3% of Group A, B and C patients, respectively (P < 0.001, P = 0.001 and P = 0.005, respectively). On addition of MTB PCR to histopathology, tuberculous lymphadenitis was diagnosed in 0.4%, 1.9% and 8.8%, respectively (Group C; P = 0.029). CONCLUSION: Routine AFB culture of needle rinse fluid was useful to increase the diagnostic yield of tuberculous lymphadenitis for all subjects who underwent EBUS-TBNA regardless of pre-procedural diagnosis in an intermediate tuberculosis (TB)-burden country. However, MTB PCR was only useful in subjects with pre-procedural diagnosis of benign pulmonary diseases.

Correction to: Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

Following publication of the original.

Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

BACKGROUND: Endosonography with needle aspiration (EBUS/EUS-NA) is recommended as the first choice for mediastinal nodal assessment in non-small cell lung cancer (NSCLC). It is important to maintain adequate negative predictive value of the procedure to avoid unnecessary additional surgical staging, but there are few studies on the influence of operator-related factors including competency on false negative results. This study aims to compare the false negative rate of individual operators and whether it changes according to accumulation of experience. METHODS: This is a retrospective study of NSCLC patients who were N0/N1 by EBUS/EUS-NA and confirmed by pathologic staging upon mediastinal lymph node dissection (n = 705). Patients were divided into a false negative group (finally confirmed as pN2/N3) and a true negative group (pN0/N1). False negative rates of six operators and whether these changed according to accumulated experience were analyzed. RESULTS: There were 111 (15.7%) false negative cases. False negative rates among six operators ranged from 8.3 to 21.4%; however, there were no statistical differences before and after adjustment for patient characteristics and procedure-related factors (P = 0.346 and P = 0.494, respectively). In addition, false negative rates did not change as each operator accumulated experience (P for trend = 0.632). CONCLUSIONS: Our data suggest that there would be no difference in false negative rates regardless of which operator performs the procedure assuming that the operators have completed a certain period of observation and have performed procedures under the guidance of an expert.

Tumor suppressor protein DAB2IP participates in chromosomal stability maintenance through activating spindle assembly checkpoint and stabilizing kinetochore-microtubule attachments.

Defects in kinetochore-microtubule (KT-MT) attachment and the spindle assembly checkpoint (SAC) during cell division are strongly associated with chromosomal instability (CIN). CIN has been linked to carcinogenesis, metastasis, poor prognosis and resistance to cancer therapy. We previously reported that the DAB2IP is a tumor suppressor, and that loss of DAB2IP is often detected in advanced prostate cancer (PCa) and is indicative of poor prognosis. Here, we report that the loss of DAB2IP results in impaired KT-MT attachment, compromised SAC and aberrant chromosomal segregation. We discovered that DAB2IP directly interacts with Plk1 and its loss inhibits Plk1 kinase activity, thereby impairing Plk1-mediated BubR1 phosphorylation. Loss of DAB2IP decreases the localization of BubR1 at the kinetochore during mitosis progression. In addition, the reconstitution of DAB2IP enhances the sensitivity of PCa cells to microtubule stabilizing drugs (paclitaxel, docetaxel) and Plk1 inhibitor (BI2536). Our findings demonstrate a novel function of DAB2IP in the maintenance of KT-MT structure and SAC regulation during mitosis which is essential for chromosomal stability.

Phosphorylation of Ku dictates DNA double-strand break (DSB) repair pathway choice in S phase.

Multiple DNA double-strand break (DSB) repair pathways are active in S phase of the cell cycle; however, DSBs are primarily repaired by homologous recombination (HR) in this cell cycle phase. As the non-homologous end-joining (NHEJ) factor, Ku70/80 (Ku), is quickly recruited to DSBs in S phase, we hypothesized that an orchestrated mechanism modulates pathway choice between HR and NHEJ via displacement of the Ku heterodimer from DSBs to allow HR. Here, we provide evidence that phosphorylation at a cluster of sites in the junction of the pillar and bridge regions of Ku70 mediates the dissociation of Ku from DSBs. Mimicking phosphorylation at these sites reduces Ku's affinity for DSB ends, suggesting that phosphorylation of Ku70 induces a conformational change responsible for the dissociation of the Ku heterodimer from DNA ends. Ablating phosphorylation of Ku70 leads to the sustained retention of Ku at DSBs, resulting in a significant decrease in DNA end resection and HR, specifically in S phase. This decrease in HR is specific as these phosphorylation sites are not required for NHEJ. Our results demonstrate that the phosphorylation-mediated dissociation of Ku70/80 from DSBs frees DNA ends, allowing the initiation of HR in S phase and providing a mechanism of DSB repair pathway choice in mammalian cells.

Real-world treatment patterns for patients 80 years and older with early lung cancer: a nationwide claims study.

BACKGROUND: Old age is an important factor that could affect the treatment of early-stage lung cancer. In this study, we evaluated the treatment patterns and outcomes of patients over the age of 80 years who had been diagnosed with early-stage lung cancer in real-world practice. METHODS: Elderly patients who were diagnosed with early-stage lung cancer between 2008 and 2016 were identified using claims data provided by the Health Insurance Review and Assessment Service. The proportion of patients who underwent surgical resection or stereotactic body radiation therapy (SBRT), practice pattern trends, and overall survival (OS) were analyzed from the population-based data. RESULTS: Over 9 years, 1,684 patients underwent surgical resection (74.9%) or SBRT (25.1%) as a localized treatment. From 2008 to 2016, the treatment modality changed: the percentage of patients who underwent surgical resection decreased from 90.6 to 71.4%, and those who underwent SBRT increased from 9.4 to 28.6%. The percentage of patients treated with SBRT increased over time (p < 0.001). The median OS was 56.4 months in the surgery group and 35.5 months in the SBRT group. The SBRT group showed worse OS compared with the surgery group (Adjusted hazard ratio, 1.44; 95% confidence interval, 1.21-1.72; p < 0.001). CONCLUSION: Changes in local treatment patterns in elderly lung cancer patients were observed and SBRT increased its role in this population. Surgical resection or SBRT should be considered the treatment of choice in elderly patients with localized lung cancer. Further prospective studies are required to elucidate the benefits of surgery and SBRT.

DNA-PKcs phosphorylates hnRNP-A1 to facilitate the RPA-to-POT1 switch and telomere capping after replication.

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) has been implicated in telomere protection and telomerase activation. Recent evidence has further demonstrated that hnRNP-A1 plays a crucial role in maintaining newly replicated telomeric 3' overhangs and facilitating the switch from replication protein A (RPA) to protection of telomeres 1 (POT1). The role of hnRNP-A1 in telomere protection also involves DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the detailed regulation mechanism has not been clear. Here we report that hnRNP-A1 is phosphorylated by DNA-PKcs during the G2 and M phases and that DNA-PK-dependent hnRNP-A1 phosphorylation promotes the RPA-to-POT1 switch on telomeric single-stranded 3' overhangs. Consequently, in cells lacking hnRNP-A1 or DNA-PKcs-dependent hnRNP-A1 phosphorylation, impairment of the RPA-to-POT1 switch results in DNA damage response at telomeres during mitosis as well as induction of fragile telomeres. Taken together, our results indicate that DNA-PKcs-dependent hnRNP-A1 phosphorylation is critical for capping of the newly replicated telomeres and prevention of telomeric aberrations.

BRCA1 modulates the autophosphorylation status of DNA-PKcs in S phase of the cell cycle.

Non-homologous end-joining (NHEJ) and homologous recombination (HR) are the two prominent pathways responsible for the repair of DNA double-strand breaks (DSBs). NHEJ is not restricted to a cell-cycle stage, whereas HR is active primarily in the S/G2 phases suggesting there are cell cycle-specific mechanisms that play a role in the choice between NHEJ and HR. Here we show NHEJ is attenuated in S phase via modulation of the autophosphorylation status of the NHEJ factor DNA-PKcs at serine 2056 by the pro-HR factor BRCA1. BRCA1 interacts with DNA-PKcs in a cell cycle-regulated manner and this interaction is mediated by the tandem BRCT domain of BRCA1, but surprisingly in a phospho-independent manner. BRCA1 attenuates DNA-PKcs autophosphorylation via directly blocking the ability of DNA-PKcs to autophosphorylate. Subsequently, blocking autophosphorylation of DNA-PKcs at the serine 2056 phosphorylation cluster promotes HR-required DNA end processing and loading of HR factors to DSBs and is a possible mechanism by which BRCA1 promotes HR.

The N-terminal region of the DNA-dependent protein kinase catalytic subunit is required for its DNA double-stranded break-mediated activation.

DNA-dependent protein kinase (DNA-PK) plays an essential role in the repair of DNA double-stranded breaks (DSBs) mediated by the nonhomologous end-joining pathway. DNA-PK is a holoenzyme consisting of a DNA-binding (Ku70/Ku80) and catalytic (DNA-PKcs) subunit. DNA-PKcs is a serine/threonine protein kinase that is recruited to DSBs via Ku70/80 and is activated once the kinase is bound to the DSB ends. In this study, two large, distinct fragments of DNA-PKcs, consisting of the N terminus (amino acids 1-2713), termed N-PKcs, and the C terminus (amino acids 2714-4128), termed C-PKcs, were produced to determine the role of each terminal region in regulating the activity of DNA-PKcs. N-PKcs but not C-PKcs interacts with the Ku-DNA complex and is required for the ability of DNA-PKcs to localize to DSBs. C-PKcs has increased basal kinase activity compared with DNA-PKcs, suggesting that the N-terminal region of DNA-PKcs keeps basal activity low. The kinase activity of C-PKcs is not stimulated by Ku70/80 and DNA, further supporting that the N-terminal region is required for binding to the Ku-DNA complex and full activation of kinase activity. Collectively, the results show the N-terminal region mediates the interaction between DNA-PKcs and the Ku-DNA complex and is required for its DSB-induced enzymatic activity.

Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian period length.

The Cryptochrome (CRY) proteins are critical components of the mammalian circadian clock and act to rhythmically repress the activity of the transcriptional activators CLOCK and BMAL1 at the heart of the clock mechanism. The CRY proteins are part of a large repressive complex, the components of which are not completely known. Using mass spectroscopy, we identified the catalytic subunit of DNA-dependent protein kinase as a CRY-interacting protein and found that loss or inhibition of this kinase results in circadian rhythms with abnormally long periods. We then identified serine 588 in the C-terminal tail of mouse CRY1 as a potential DNA-PK phosphorylation site but surprisingly found that the phosphomimetic mutation S588D also results in long period rhythms, similar to the loss of DNA-PK. Consistent with this, we found that phosphorylation of this site is increased in cells lacking DNA-PK, suggesting that DNA-PK negatively regulates the phosphorylation of this site most likely through indirect means. Furthermore, we found that phosphorylation of this site increases the stability of the CRY1 protein and prevents FBXL3-mediated degradation. The phosphorylation of this site is robustly rhythmic in mouse liver nuclei, peaking in the middle of the circadian day at a time when CRY1 levels are declining. Therefore, these data suggest a new role for the C-terminal tail of CRY1 in which phosphorylation rhythmically regulates CRY1 stability and contributes to the proper circadian period length.

Clinical value of endobronchial ultrasound findings for predicting nodal metastasis in patients with suspected lymphadenopathy: a prospective study.

We evaluated whether sonographic findings can provide additional diagnostic yield in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), and can more accurately predict nodal metastasis than chest computed tomography (CT) or positron emission tomography (PET)/CT scans. EBUS-TBNA was performed in 146 prospectively recruited patients with suspected thoracic lymph node involvement on chest CT and PET/CT from June 2012 to January 2013. Diagnostic yields of EBUS finding categories as a prediction model for metastasis were evaluated and compared with findings of chest CT, PET/CT, and EBUS-TBNA. In total, 172 lymph nodes were included in the analysis: of them, 120 were malignant and 52 were benign. The following four EBUS findings were predictive of metastasis: nodal size ≥10 mm, round shape, heterogeneous echogenicity, and absence of central hilar structure. A single EBUS finding did not have sufficient diagnostic yield; however, when the lymph node had any one of the predictive factors on EBUS, the diagnostic yields for metastasis were higher than for chest CT and PET/CT, with a sensitivity of 99.1% and negative predictive value of 83.3%. When any one of predictive factors is observed on EBUS, subsequent TBNA should be considered, which may provide a higher diagnostic yield than chest CT or PET/CT.

Association between commuting time and work-related low back pain with respect to sports and leisure activities in Korean workers.

Long commuting times can induce work-related low back pain (LBP), which can be exacerbated by reduced sports and leisure activities. However, there is a lack of empirical research on commuting time and work-related LBP in Korea. In this study, we aimed to investigate the relationship between commuting time and work-related LBP as well as the effect of sports and leisure activities on Korean workers. We utilized data from the sixth Korean Working Conditions Survey to analyze the relationship between commuting time and work-related LBP using multivariable logistic regression. The total number of included workers was 28,202. Workers without sports and leisure activities, and long commuting times (40-59, 60-79, and ≥80 min) showed significantly higher odds ratios for work-related LBP (1.29 [95% Confidence intervals=1.12-1.49], 1.42 [1.22-1.65], and 1.96 [1.68-2.28], respectively). However, in workers with sports and leisure activities, the results were significant only for commuting times of 60-79 and ≥80 min (1.41 [1.13-1.75], 1.60 [1.28-1.99], respectively). Long commuting times were associated with work-related LBP, and engagement in sports and leisure activities was found to play a role in mitigating the impact among Korean wage workers.

3D airway geometry analysis of factors in airway navigation failure for lung nodules.

BACKGROUND: This study aimed to quantitatively reveal contributing factors to airway navigation failure during radial probe endobronchial ultrasound (R-EBUS) by using geometric analysis in a three-dimensional (3D) space and to investigate the clinical feasibility of prediction models for airway navigation failure. METHODS: We retrospectively reviewed patients who underwent R-EBUS between January 2017 and December 2018. Geometric quantification was analyzed using in-house software built with open-source python libraries including the Vascular Modeling Toolkit ( http://www.vmtk.org ), simple insight toolkit ( https://sitk.org ), and sci-kit image ( https://scikit-image.org ). We used a machine learning-based approach to explore the utility of these significant factors. RESULTS: Of the 491 patients who were eligible for analysis (mean age, 65 years +/- 11 [standard deviation]; 274 men), the target lesion was reached in 434 and was not reached in 57. Twenty-seven patients in the failure group were matched with 27 patients in the success group based on propensity scores. Bifurcation angle at the target branch, the least diameter of the last section, and the curvature of the last section are the most significant and stable factors for airway navigation failure. The support vector machine can predict airway navigation failure with an average area under the curve of 0.803. CONCLUSIONS: Geometric analysis in 3D space revealed that a large bifurcation angle and a narrow and tortuous structure of the closest bronchus from the lesion are associated with airway navigation failure during R-EBUS. The models developed using quantitative computer tomography scan imaging show the potential to predict airway navigation failure.