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Table S1 and Table S2- Patients' characteristics. Table S3 - Cell lines. Table S4 - Antibodies used. Table S5 - Expression of PD-L1 and Galectin-9 in lung cancer. Table S6 - Expression of XAGE1 in lung cancer. Table S7 - Cut-off values for each T-cell parameter. Table S8 - Standardized coefficients in discriminant functions. Table S9 - Univariate and multivariate analysis.

The histopathological distinction of lung adenocarcinoma (LADC) subtypes is subject to high inter-observer variability, which can compromise the optimal assessment of the patient prognosis. Therefore, this study developed convolutional neural networks (CNNs) capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the LADC tumour grades established recently by the International Association for the Study of Lung Cancer pathology committee. Consensus LADC ground truth histopathological images were obtained from seventeen expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained with EfficientNet b3 architecture to predict eight different LADC classes (lepidic, acinar, papillary, micropapillary, solid, invasive mucinous adenocarcinoma, other carcinoma types, and no carcinoma cells). Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1-scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models. Moreover, the grading prediction of one of the trained models was more accurate than those of 14 out of 15 pulmonary pathologists involved in the study (p=0.0003). Both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained CNNs improve the diagnostic accuracy of the pathologist, standardise LADC subtype recognition, and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Context.— The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability. Objective.— To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications. Design.— Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 18 international expert lung pathologists. Each image was classified into one or several lung adenocarcinoma subtypes. Results.— Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes. Conclusions.— Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.

Objective To determine whether autonomic dysfunction in neurosarcoidosis is associated with anti-ganglionic acetylcholine receptor (gAChR) antibodies, which are detected in autoimmune autonomic ganglionopathy. Methods We retrospectively extracted cases of sarcoidosis from 1787 serum samples of 1,381 patients between 2012 and 2018. Anti-gAChR antibodies against the α3 and β4 subunit were measured by luciferase immunoprecipitation to confirm the clinical features of each case. We summarized literature reviews of neurosarcoidosis with severe dysautonomia to identify relevant clinical features and outcomes. Results We extracted three new cases of neurosarcoidosis with severe dysautonomia, among which two were positive for anti-gAChR antibodies: Case 1 was positive for antibodies against the β4 subunit, and Case 2 was positive for antibodies against both the α3 and β4 subunits. We reviewed the cases of 15 patients with neurosarcoidosis and severe dysautonomia, including the three cases presented herein. Orthostatic hypotension and orthostatic intolerance were the most common symptoms. Among the various types of neuropathy, small fiber neuropathy (SFN) was the most prevalent, with seven of nine cases exhibiting definite SFN. Six of eight cases had impaired postganglionic fibers, of which the present three cases revealed abnormality of 123I-MIBG myocardial scintigraphy. Of the 11 cases, 10 were responsive to immunotherapy, except one seropositive case (Case 2). Conclusions The presence of gAChR antibodies may constitute one of the mechanisms by which dysautonomia arises in neurosarcoidosis.

Background Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP. Methods Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis. Results Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11–0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13–0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value. Conclusions BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.

Background Adequate tumor tissue is required to make the best treatment choice for non-small cell lung cancer (NSCLC). Transbronchial biopsy (TBB) by endobronchial ultrasonography with a guide sheath (EBUS-GS) is useful to diagnose peripheral lung lesions. The data of tumor cell numbers obtained by two different sizes of GSs is limited. We conducted this study to investigate the utility of a large GS kit to obtain many tumor cells in patients with NSCLC. Methods Patients with a peripheral lung lesion and suspected of NSCLC were prospectively enrolled. They underwent TBB with a 5.9-mm diameter bronchoscope with a large GS. When the lesion was invisible in EBUS, we changed to a thinner bronchoscope and TBB was performed with a small GS. We compared the tumor cell number prospectively obtained with a large GS (prospective large GS group) and those previously obtained with a small GS (small GS cohort). The primary endpoint was the tumor cell number per sample, and we assessed characteristics of lesions that could be obtained by TBB with large GS. Results Biopsy with large GS was performed in 55 of 87 patients (63.2%), and 37 were diagnosed with NSCLC based on histological samples. The number of tumor cells per sample was not different between two groups (658±553 vs. 532±526, estimated difference between two groups with 95% confidence interval (CI); 125 (-125–376), p = 0.32). The sample size of the large GS group was significantly larger than that of the small GS cohort (1.75 mm2 vs. 0.83 mm2, estimated difference with 95% CI; 0.92 (0.60–1.23) mm2, p = 0.00000019). The lesion involving a third or less bronchus generation was predictive factors using large GS. Conclusions The sample size obtained with large GS was significantly larger compared to that obtained with small GS, but there was no significant difference in tumor cell number. The 5.9-mm diameter bronchoscope with large GS can be used for lesions involving a third or less bronchus generation.

Background: Impact of bronchoalveolar lavage (BAL) lymphocytosis >15% on the prognosis of chronic idiopathic interstitial pneumonias other than idiopathic pulmonary fibrosis (non-IPF) has never been evaluated. Methods: Japanese chronic non-IPF patients treated with corticosteroids were identified using the nationwide registry along with multidisciplinary discussion (MDD). We compared the clinical, radiological and pathological features, and outcomes between patients with BAL lymphocytosis >15% and those with BAL lymphocytes ≤15%. Results: Of the 110 patients with chronic non-IPF, 47 (42.7%) had BAL lymphocytosis >15%. The most prevalent MDD diagnosis was unclassifiable IIPs (64.5%), followed by iNSIP (22.7%). Immunosuppressants were administered in 69 (62.7%) patients. There were no significant difference in HRCT and pathological patterns, MDD diagnoses, and treatment regimens between the two groups. One-year changes in KL-6 and FVC % predicted were significantly better in patients with BAL lymphocytosis >15% than those with BAL lymphocytes ≤15%. Patients with BAL lymphocytosis >15% had longer OS than those with BAL lymphocytes ≤15% (Log-rank test, p =0.019). In multivariate analysis, BAL lymphocytosis >15% was a significant prognostic factor for overall survival (HR: 0.37; 95% CI, 0.16-0.87; p =0.022), in addition to FVC % predicted and interstitial pneumonia with autoimmune features. Conclusions: BAL lymphocytosis >15% is associated with favorable outcome in chronic non-IPF. Evaluation of BAL lymphocytes would be helpful to identify corticosteroid-effective patients.

Nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP) are major subtypes of idiopathic interstitial pneumonias (IIPs) and closely related to connective tissue diseases (CTDs). "NSIP with OP overlap" is a controversial finding that has recently appeared in the criteria of interstitial pneumonia with autoimmune features (IPAF). However, details of this controversial entity are not well known.To determine the frequency of "NSIP with OP overlap" pattern in IIPs and to identify differences from idiopathic NSIP (iNSIP).In 524 patients with interstitial pneumonia from 39 institutes who underwent surgical lung biopsy, 444 were diagnosed as IIPs by a multidisciplinary discussion meeting via a cloud-based integrated database. Among these patients, 44 (9.9%) who had iNSIP and 21 (4.7%) with histopathologically-defined "NSIP with OP overlap" pattern (a pathological NSIP and OP pattern, but without a UIP pattern) were retrospectively studied.Patients with "NSIP with OP overlap" pattern showed a significantly greater extent of consolidation (p 0.001), more subpleural ground glass attenuation (p = 0.036), and more peripheral + bronchovascular distribution (p = 0.009) on high-resolution computed tomography than those with iNSIP. The incidences of newly-developed CTDs during follow-up was similar between the groups and polymyositis/dermatomyositis was the most frequent CTD in both groups. Nearly half of the patients fulfilled IPAF criteria, but no significant difference was found between iNSIP and "NSIP with OP overlap" pattern (47.7% vs. 42.9, p = 0.712). The incidence of acute exacerbation and the survival rates were similar between the groups.The incidence of "NSIP with OP overlap" pattern is 4.7% in IIPs. The frequency of newly-developed CTDs during follow-up, mainly polymyositis/dermatomyositis, the frequency of acute exacerbation, and the survival rate in "NSIP with OP overlap" pattern are similar to those of iNSIP.

Context.—In 2013, the revised American Thoracic Society and European Respiratory Society classification of idiopathic interstitial pneumonias (IIPs) described 2 rare IIPs and 2 rare histologic patterns. Because of the rarity of the disease, there is limited evidence related to the histology. Because the rare histologic patterns are provisional criteria, no unanimous consensus on histologic diagnostic criteria has yet been reached.Objective.—To review the histologic features for rare IIPs and rare histologic patterns, and to provide diagnostic aids and discuss the differential diagnosis.Data Sources.—Published peer-reviewed literature and the authors' personal experience.Conclusions.—Following the publication of the international consensus classification, evidence regarding rare IIPs and rare histologic patterns has accumulated to some extent, although to date the amount remains insufficient and further evidence is required. Because the diagnosis is sometimes challenging, a multidisciplinary approach represents the gold standard in reaching an accurate diagnosis for these rare disorders.

The Nemegt locality is one of the most famous dinosaur localities in Mongolia ever since the site was discovered in 1946. It yields abundant dinosaur skeletons; however, little attention had been given to dinosaur footprints at the locality. The only Nemegt dinosaur footprint study focused on descriptions of the footprints, gave only a few taxonomic implications, and provided no comparison with other dinosaur tracksites. This study reports newly recorded dinosaur footprints (hadrosaurs, sauropods, and theropods) at the Nemegt locality during the Nemegt Educational Expedition of 2016. A single footprint-bearing horizon that extends several kilometres was examined within the Nemegt Formation to determine the ichno-taxonomic assemblage of the Nemegt dinosaurs. A significant difference was identified between taxonomic compositions based on skeletal remains and ichno-taxonomic compositions based on footprints. Although the vast majority of the skeletal elements collected in the area belong to theropods, the footprints suggest that the Nemegt locality was dominated by herbivorous dinosaurs. This suggests that the previously inferred Tarbosaurus dominant taxonomic composition at the Nemegt locality is a result of a preservational bias. The size distribution of the newly studied footprints suggest that the Nemegt hadrosaurs had an adult-dominant and multigenerational population structure. Comparisons with dinosaur tracksites at the Cantwell (Alaska, USA) and Tremp (Spain) formations show that the population structure and body sizes of the Nemegt hadrosaurs were similar to those of the high-latitude Cantwell hadrosaurs. It suggests that the Nemegt area was more open and had higher plant productivity than the Tremp area.

The Upper Cretaceous Nemegt Formation of Mongolia is rich in well-preserved dinosaurs and Ornithomimosauria is one of the most common taxa in the formation. Three ornithomimosaur taxa, Anserimimus planinychus, Deinocheirus mirificus, and Gallimimus bullatus, have been discovered from the formation so far. However, the recently discovered specimens suggest there is even greater morphological variation of ornithomimosaurs in the Nemegt Formation than are presently recognized. This study focuses on the structures of manual elements among Nemegt ornithomimosaurs and reveals their remarkable diversity. The manual structures of seven individuals, including aforementioned three known taxa and four new individuals, are morphologically distinct from each other. Numerical analyses on metacarpals, phalanges, and unguals also support high morphological diversity of the Nemegt ornithomimosaurs. The large diversity of manual morphology may be related to large variety of palaeoecological niches were prevailed in the Nemegt ecosystem.

Asian hesperornithiforms are extremely rare in contrast to the much more abundant record from North America. In Asia, these fossil birds are only known from fragmentary materials from Mongolia. Here we describe the skeletal remains of a new hesperornithiform Chupkaornis keraorum gen. et sp. nov. from the Upper Cretaceous Kashima Formation (Coniacian to Santonian) of the Yezo Group in Mikasa City, Hokkaido, Japan. This is the best-preserved hesperornithiform material from Asia and it is the first report of hesperornithiforms from the eastern margin of the Eurasian continent. Chupkaornis has a unique combination of characters: finger-like projected tibiofibular crest of femur, deep, emarginated lateral excavation with a sharply defined edge of the ventral margin of the thoracic vertebrae, and the heterocoelous articular surface of the thoracic vertebrae. Our new phylogenetic analysis revises the phylogenetic relationships of Hesperornithiformes. In contrast to previous studies, Enaliornis is assigned as the...

Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease often accompanied by skeletal muscle wasting. We investigated whether skeletal muscle mass and muscle attenuation on computed tomography (CT) are predictors of mortality in IPF patients, using a nationwide cloud-based database and web-based multidisciplinary discussion (MDD) system. Methods IPF patients diagnosed using MDD from April 2009 to March 2014 were included. We analyzed the cross-sectional area (CSA) of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA), muscle attenuation of the ESM (ESMMA), and PM (PMMA) on single-slice axial CT. Survival probability was assessed using the Kaplan–Meier method and compared by the log-rank test. Multivariate Cox proportional hazards models were used to evaluate the relationship among the ESMCSA, PMCSA, ESMMA, PMMA, clinical parameters, and prognosis. Results A total of 199 IPF patients were enrolled. Seventy-four patients died during the study period and the most frequent cause was acute exacerbation (13.1%). The group with the lowest quartile of ESMCSA had significantly worse survival than other groups (P = 0.009). Survival rates of the groups with the lowest quartile of PMCSA, lower ESMMA, and lower PMMA did not differ from those of other groups. According to multivariate analysis, ESMCSA Conclusions Low ESMCSA on CT images may be a strong risk factor for all-cause mortality in IPF patients based on MDD diagnosis.

We herein report the case of a 74-year-old woman with a lung tumor. She presented with complaints of blurred and rapid, progressively impaired vision. A visual field examination revealed bilateral concentric contraction of the visual field and a ring scotoma in the right eye. She was diagnosed with cancer-associated retinopathy (CAR) combined with large-cell neuroendocrine carcinoma (LCNEC) of the lung via a visual field examination and underwent thoracoscopic surgery. CAR has been mostly associated with small-cell lung cancer (SCLC). Combined LCNEC is relatively rare and accounts for 10.6% of all LCNECs. This is the first case report of CAR-combined LCNEC.

Thoracic diseases in patients with systemic lupus erythematosus (SLE), especially interstitial pneumonia (SLE-IP), are rare and have been poorly studied. The aims of this multicentre study were to evaluate SLE-IP and elucidate its clinical characteristics and prognosis. Fifty-five patients with SLE-IP who had attended the respiratory departments of participating hospitals were retrospectively evaluated in this multicentre study. Clinical information, high-resolution computed tomography (HRCT), and surgical lung biopsy/autopsy specimens were analysed by respiratory physicians, pulmonary radiologists, and pulmonary pathologists. IP patterns on HRCT and lung specimens were classified based on the international classification statement/guideline for idiopathic interstitial pneumonias. The most frequent form of SLE-IP at diagnosis was chronic IP (63.6%), followed by subacute (20.0%), and acute IP (12.7%). Radiologically, the most common HRCT pattern was “Unclassifiable” (54%). Histologically, “Unclassifiable” was the most frequently found (41.7%) among 12 patients with histologically proven IP. Interestingly, accompanying airway diseases were present in nine of these patients (75%). In multivariate analysis, current smoking (hazard ratio [HR] 6.105, p = 0.027), thrombocytopenia (HR 7.676, p = 0.010), anti-double-strand DNA titre (HR 0.956, p = 0.027), and nonspecific interstitial pneumonia (NSIP) + organizing pneumonia (OP) pattern on HRCT (vs. NSIP, HR 0.089, p = 0.023) were significant prognostic factors. In conclusion, chronic IP was the most frequent form of IP in patients with SLE-IP, and “Unclassifiable” was the commonest pattern radiologically and histologically.

BACKGROUND AND OBJECTIVE Acute exacerbation (AE) is a severe complication of idiopathic pulmonary fibrosis (AE-IPF). In 2016, an international working group revised its definition and diagnostic criteria; however, few studies have assessed the frequency and prognosis of AE in patients with other fibrotic interstitial lung diseases (FILD). METHODS We used data from 1019 consecutive interstitial lung disease (ILD) patients initially evaluated between January 2008 and July 2015. All subject diagnoses were made by multidisciplinary discussion in December 2018. ILD was categorized as IPF (n = 462) and other FILD which included non-specific interstitial pneumonia (n = 22), chronic hypersensitivity pneumonitis (n = 29), connective tissue disease-associated ILD (n = 205) and unclassifiable ILD (n = 209). Using the 2016 definition of AE-IPF, we identified all subjects with an AE. RESULTS During the observational period, 193 patients experienced a first AE (AE-FILD n = 69, AE-IPF n = 124). The time to first AE was significantly longer in FILD than IPF (log-rank test, P

Recent studies have suggested that in patients with an idiopathic interstitial pneumonia (IIP), a probable usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT) is sufficient to diagnose idiopathic pulmonary fibrosis (IPF) without histopathology.We retrospectively compared the prognosis and time to first acute exacerbation (AE) in IIP patients with a UIP and a probable UIP pattern on initial chest CT.One hundred and sixty IIP patients with a UIP pattern and 242 with a probable UIP pattern were identified. Probable UIP pattern was independently associated with longer survival time (adjusted hazard ratio 0.713, 95% CI 0.536–0.950; p=0.021) and time to first AE (adjusted hazard ratio 0.580, 95% CI 0.389–0.866; p=0.008). In subjects with a probable UIP pattern who underwent surgical lung biopsy, the probability of a histopathological UIP pattern was 83%. After multidisciplinary discussion and the inclusion of longitudinal behaviour, a diagnosis of IPF was made in 66% of cases. In IPF patients, survival time and time to first AE were not associated with CT pattern. Among subjects with a probable UIP pattern, compared to non-IPF patients, survival time and time to first AE were shorter in IPF patients.In conclusion, IIP patients with a probable UIP pattern on initial chest CT had a better prognosis and longer time to first AE than those with a UIP pattern. However, when baseline data and longitudinal behaviour provided a final diagnosis of IPF, CT pattern was not associated with these outcomes. This suggests diagnostic heterogeneity among patients with a probable UIP pattern.

In management of the FDC (Fault Detection and Classification) alarm threshold, sensor drift after maintenance has been big and major challenge. Especially in etching area where has relatively short maintenance (cleaning) cycle and many chambers and recipes (our fab is high-mix low-volume type.). We developed auto threshold re-calculate system practical and easily introduce. Using the system we successfully reduce needed cost of re-calculate the threshold and loss of manufacturing time.

We study Bi-adsorbed In atomic chains on Si(111) in order to design a one-dimensional (1D) Rashba system using first-principles calculations. From the band dispersions and spin textures, we find that this system shows 1D giant Rashba splittings. The Rashba parameters of several structures in this system are comparable with other Rashba systems. Depending on the adsorption structure, this system also shows remarkable features such as a large out-of-plane spin polarization, the reversal of spin polarization in the Rashba bands, and a metal-insulator transition. We propose a mechanism to generate a nondissipative spin current by the gap opening due to an avoided crossing of Rashba bands. This mechanism is suitable for spintronic applications without requiring an external magnetic field.

Prediction of the Curie temperature is of significant importance for the design of ferromagnetic materials. One of the most widely used methods to estimate the Curie temperature from first principles relies on a spin Hamiltonian, for example, the Heisenberg Hamiltonian, and exchange coupling parameters obtained by first-principles calculations at zero temperature. Even though there have been attempts to include the effects of magnetism on phonons, the influence of magnetism-dependent phonons on magnetism has been disregarded in the theoretical estimation of the Curie temperature. Here, we propose a first-principles thermodynamic approach to minimise the total free energy considering both the influences of magnetism on phonons and the feedback effect from phonons to magnetism. By applying our scheme to body-centered cubic Fe, we find a significant reduction of the Curie temperature due to the feedback effect. This result indicates the importance of the feedback effect for a quantitative description of finite-temperature magnetism. In addition, we point out that the reduction in the theoretical Curie temperature arises in a wide range of ferromagnetic materials that exhibit phonon softening due to magnetic disordering.

Purpose: Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. Patients and methods: We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. Results: In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. Conclusion: A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema., International Journal of Chronic Obstructive Pulmonary Disease, 11(1), pp.2287-2294; 2016

Hideji Otani,1 Tomonori Tanaka,2 Kiyoshi Murata,1 Junya Fukuoka,2 Norihisa Nitta,1 Yukihiro Nagatani,1 Akinaga Sonoda,1 Masashi Takahashi3 1Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, 2Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, 3Department of Radiology, Yujin-Yamazaki Hospital, Takegahana-cho, Hikone, Shiga, Japan Purpose: To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Patients and methods: Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. Results: The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. Conclusion: SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema. Keywords: pulmonary emphysema, smoking, usual interstitial pneumonia, honeycombing, smoking-related interstitial fibrosis, airspace enlargement with fibrosis

The Kamitaki Locality in the Albian Ohyamashimo Formation in the eastern Hyogo Prefecture of southwestern Japan is among the richest Lower Cretaceous fossil egg sites in the world. So far, eggshells of five different ootaxa, one ornithopod and four theropods, have been identified from the Kamitaki Bonebed Quarry. Although previous discoveries of egg remains were limited to isolated eggshell fragments, here we report on the discovery of a nearly complete egg, several partial eggs, as well as numerous eggshell fragments from horizons of the newly excavated Kamitaki Egg Quarry that are 5.5–6.75 m above the Kamitaki Bonebed Quarry. Taphonomical investigations indicate that the new site preserves the remnants of an in-situ nest of Himeoolithus murakamii oogen. et oosp. nov., mixed with scattered and isolated eggshell fragments of other non-avian theropod ootaxa, including Nipponoolithus ramosus, Prismatoolithus sp., and Subtiliolithus hyogoensis oosp. nov. The most abundant ootaxon at the quarry, Himeoolithus, is represented by four eggs and over 1300 scattered eggshell fragments. Himeoolithus is the smallest non-avian theropod egg known to date (9.9 g in estimated mass) and exhibits an unusually elongated shape (length:width ratio of 2.25) for such as small egg. The presence of six dinosaur ootaxa from the two quarries at the Kamitaki Locality reveals a hidden diversity of small dinosaurs, particularly non-avian theropods, in the Hyogo region and indicates the area was utilized for nesting by various small dinosaur species at the end of the Early Cretaceous.

We present first-principles phonon calculations for ferromagnetic and paramagnetic (disordered local moment) states in B2-type (FeCo, MnNi) and L10-type (CoPt, FePt, FePd) materials. The calculatio...

Asian hesperornithiforms are extremely rare in contrast to North American records; thus, their diversity in Asia during the Cretaceous is unclear. Maastrichtian hesperornithiform materials have been reported from both fluvial and marine deposits in North America but only from fluvial deposits in Asia. Asian hesperornithiforms from Maastrichtian deposits have been considered as freshwater taxa because of their occurrence from fluvial sediments and their histological features. Here, we report the first hesperornithiform record from marine Maastrichtian deposits in Asia. It is represented by an isolated left tibiotarsus from the inter-arc basin deposit of the Kita-ama Formation (lower Maastrichtian), Izumi Group of southwest Japan. It has a shallow tibial incision, fibular crest extending to the mid shaft, and laterally angled lateral articular surface. Although its phylogenetic position within Hesperornithiformes is ambiguous, these characters are similar to non-hesperornithid hesperornithiforms. Unossified proximal and distal epiphyses indicate that this individual was immature. A remarkably thick cortical area of the tibiotarsus suggests that this hesperornithiform was a sea-dwelling bird and that the habitat of this group during the Maastrichtian extended to both terrestrial and marine environments in Asia and North America.

Dewatering is a common engineering practice to secure the accessibility during the construction and operational phases of tunnels. It is thus important to accurately estimate the amount of groundwater flow into underground openings for the design and safe operation of tunnels. Numerical models need to be used to estimate groundwater flow into openings for given heterogeneity and regional hydrologic boundary conditions typically by assuming that the atmospheric pressure is maintained along open wall faces. As the scale of openings can be small as tens of centimeters, while models need to incorporate the regional hydrologic conditions, it is often practically impossible to explicitly represent the three-dimensional (3D) geometry of openings within numerical models. For the safety assessment of deep geological repositories of spent nuclear fuels, for example, complex configurations and geometry of various tunnels such as construction, access, ventilation, and deposition tunnels often need to be approximated as one-dimensional (1D) lines in 3D models. The application of a simple Dirichlet boundary condition along a set of tunnel nodes may yield inaccurate solutions due to geometric simplifications and coarse discretization. This study derives an appropriate boundary condition that can be applied to 1D tunnel segments to improve the accuracy when simulating inflow into openings. A third-type tunnel boundary condition is suggested to correct the difference between known wall pressure and the pressure simulated at tunnel nodes. Improvement in the precision of the solutions is demonstrated by comparing the numerical solutions using the new boundary condition with analytic solutions, and with numerical solutions when the 3D tunnel geometry is explicitly simulated. It is also shown that the formulation can be easily extended to incorporate the high permeability excavation damaged zone and the low permeability grouted zone in the tunnel vicinity. The applicability of the tunnel boundary condition is demonstrated using an example of a hypothetical deep geologic repository system consisting of various types of tunnels located in a hypothetical crystalline coastal aquifer.

Background: Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare interstitial lung disease characterised by unique radiological and pathological findings. However, pathological evaluations are available only in a limited number of patients. Therefore, several clinical diagnostic criteria have been proposed. Nevertheless, the applicability of these criteria has not yet been validated. Moreover, the clinical course of iPPFE and its prognosis have not yet been completely elucidated.Methods: The present study assessed previously proposed clinical diagnostic criteria by comparing the clinical features between pathologically diagnosed iPPFE (p-iPPFE) and clinically diagnosed iPPFE (c-iPPFE). Subsequently, the clinical features of iPPFE were characterized and compared with those of idiopathic pulmonary fibrosis (IPF, n=323).Results: Clinical characteristics of c-iPPFE (n=27) and p-iPPFE (n=35) were similar. No significant difference was observed in terms of prognosis between c-iPPFE and p-iPPFE. The number of patients with iPPFE (both c-iPPFE and p-iPPFE) who developed lung cancer was significantly lower than that of patients with IPF. However, acute exacerbation (AE) showed similar incidence in patients with iPPFE and IPF. Survival of patients with iPPFE was significantly worse than that of patients with IPF (5-year survival rate: 38.5% vs. 63.5%, p

Cap polyposis is a rare gastrointestinal disease characterized by multiple inflammatory polyps located between the distal colon and the rectum. Despite the lack of clarity regarding its pathogenesis, mucosal prolapse, chronic inflammatory responses, and Helicobacter pylori infection are considered key contributors to the development of this disease entity. Although it is now generally accepted that dysbiosis of gut microbiota is associated with intestinal and extra-intestinal diseases, alterations of intestinal microbiota have been poorly defined in cap polyposis. Here, we report a patient with H. pylori-negative cap polyposis who was successfully treated with antibiotics and exhibited dramatic alterations in intestinal microbiota composition after antibiotic treatment. The patient was treated with oral administration of ampicillin and metronidazole and showed regression of cap polyposis 6 months after antibiotic treatment. Fecal microbiota analysis using the next-generation sequencing technology revealed a significant alteration in the intestinal microbiota composition following antibiotic treatment—a marked reduction of Blautia, Dorea, and Sutterella was observed concomitant with a marked increase in Fusobacterium. These data suggest that cap polyposis may originate from dysbiosis and that microbiome-targeted therapy may be useful in this disorder.

We report an educational autopsy case of combined pulmonary fibrosis and emphysema. Radiological patterns of the upper lung were considered as mostly emphysema, but pathological observation revealed significant interstitial fibrosis of usual interstitial pneumonia as a major pathology. The patient eventually developed acute exacerbation of background interstitial pneumonia. Careful radiological and pathological correlation of the current case indicates that regions with distal acinar emphysema on computed tomography image may possess histologically marked dense fibrosis of lethal interstitial pneumonia., International Journal of Chronic Obstructive Pulmonary Disease, 10(1), pp.1299-1303; 2015