Search

Generally, Cryptococcus initially infects the respiratory tract, but can spread, eventually crossing the blood-brain barrier (BBB) and causing meningitis or meningoencephalitis. Specifically, Cryptococcus invades the vascular endothelial cells of the BBB, from which it enters the brain. The main mechanisms through which Cryptococcus crosses the BBB are transcellular traversal, the paracellular pathway, and via Trojan horse. In this paper, the mechanisms by which Cryptococcus crosses the BBB were explained in detail. In addition to pathways of entry to the brain, this paper presents a discussion on some rare cryptococcal infections and provides some insights for future research directions. [ABSTRACT FROM AUTHOR]

Cryptococcus is a family of strongly infectious pathogens that results in a wide variety of symptoms, particularly threatening the patients undergoing the immune‐deficiency or medical treatment. Rapidly identifying Cryptococcus subtypes and accurately quantifying their contents remain urgent needs for infection control and timely therapy. However, traditional detection techniques heavily rely on expensive, specialized instruments, significantly compromising their applicability for large‐scale population screening. In this work, we report a portable microwell array chip platform integrated with a deep learning‐based image recognition program, which enables rapid, precise quantification of the specific subtypes of Cryptococcus. The platform features four zones of microwell arrays preloaded with the subtype‐targeted CRISPR–Cas12a system that avoid dependence on slow, instrumental‐mediated target amplification, achieving rapid (10 min), high specificity for identifying the sequence of Cryptococcus. The deep learning‐based image recognition program utilizing segment anything model (SAM) significantly enhances automation and accuracy in identifying target concentrations, which eventually achieves ultra‐low limit of detection (0.5 pM) by personal smartphones. This platform can be further customized to adapt to various scenarios in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Pulmonary mucinous adenocarcinoma is a special type of lung cancer. Its imaging manifestations are diverse, which brings challenges to clinical diagnosis. However, its formation mechanism is unclear. Objective: The objective of this study is to analyse the relevant mechanisms of the formation of pulmonary mucinous adenocarcinoma by observing its different imaging and pathological manifestations. Data and methods: Retrospective analysis was conducted on imaging manifestations and pathological data of 103 patients with pulmonary mucinous adenocarcinoma confirmed intraoperatively or pathologically. Results: Forty‐three patients had pulmonary mucinous adenocarcinoma with a solitary nodule/mass, 41 patients with localized pneumonia and 19 patients with diffuse pneumonia. Their CT manifestations included 'falling snowflake sign', ground‐glass opacity close to the heart, vacuous signs/honeycombing and withered tree branches. Under the microscope, all the three types of pulmonary mucinous adenocarcinoma had visibly formed mucus lakes but were made of tumour cells with totally different shapes, which included the goblet‐like shape (tall column‐like shape) and quasi‐circular shape. Tall column‐shaped tumour cells were negative or weakly positive for thyroid transcription factor‐1 (TTF‐1) and strongly positive for ALK mutation, whereas quasi‐circular tumour cells were positive for TTF‐1 and less positive for ALK mutation. Conclusion: The different imaging manifestations of mucinous adenocarcinoma are possibly due to the different amounts or viscosity of mucus produced, and the mechanisms of its formation may include (1) tumour cells in different shapes have different abilities to produce mucus; (2) tumours in different stages produce different amounts or viscosity of mucus; and (3) the TTF‐1 and ALK genes affect the production of mucus. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules. Materials and methods: The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis. Results: Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037). Conclusions: In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation. [ABSTRACT FROM AUTHOR]

The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non‐small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune‐related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ‐specific irAEs in patients with NSCLC and provide an in‐depth analysis of recent advancements in understanding the mechanisms driving ICI‐induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. Methods: The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. Results: 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. Conclusion: We found that glucocorticoid 1–2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored. [ABSTRACT FROM AUTHOR]

Background: Part-solid nodules (PSNs) have gradually shifted to defining special clinical subtypes. Commonly, the solid portions of PSNs show various radiological morphologies, of which the corresponding pathological basis and prognosis are unclear. We conducted a radiological-pathological evaluation to determine the histopathologic basis of different consolidation radiographic morphologies related to prognosis.Materials and Methods: A cohort of 275 patients with a surgical pathological diagnosis of lung adenocarcinoma were enrolled. Preoperative computed tomography (CT) images of the PSNs were recorded and assessed. A panel of 103 patients with complete pathological specimens was selected to examine the radiological-pathological associations, and follow-up was performed to identify the prognosis.Results: Of the 275 patients, punctate consolidation was observed radiologically in 43/275 (15.7%), stripe consolidation in 68/275 (24.7%), and irregular consolidation in 164/275 (59.6%) patients. The radiological morphology of the solid components was significantly associated with the histopathological subtypes (P < 0.001). Visual punctate solid components on CT correlated with tertiary lymphoid structures, stripe solid components on CT correlated with fibrotic scar, and irregular solid components on CT correlated with invasion. PSNs with regular consolidation had a better prognosis than those with irregular consolidation.Conclusion: Radiological morphology of solid components in PSNs can indicate the pathological basis and is valuable for prognosis. In particular, irregular solid components in PSNs usually indicate serious invasive growth, which should be taken with caution during assessment. [ABSTRACT FROM AUTHOR]

Objectives: There are increasing numbers of studies of pleural tags (PTs). The purpose of this case series was to classify the PTs in patients with peripheral pulmonary adenocarcinoma based on radiologic-pathologic comparison and to study the prognosis.Methods: The clinical, imaging, pathological and prognostic data of 161 patients with peripheral pulmonary adenocarcinoma in three hospitals were analyzed retrospectively. We classified PTs using computed tomography (CT) for pathologic comparison.Results: According to the relationship between tumors and pleural on CT images, PTs were classified into four types: type 1, one or more linear pleural tag; type 2, one or more linear pleural tag with soft tissue component at the pleural end; type 3, one soft tissue cord-like pleural tag; type 4, directly abutting the visceral pleura, pulling or pushing the visceral pleura. In these PTs, the incidence of visceral pleural invasion (VPI) was high in type 2 (46.88%) and type 3 (56.41%) of PTs. Our prognostic analysis showed that micropapillary or solid histological subtype (HR = 5.766, 95% CI: 1.435-23.159, P = 0.014) and type 3 of PTs (HR = 11.058, 95% CI: 1.349-90.623, P = 0.025) were two independent risk factors for tumor progression.Conclusions: PT is a risk factor for poor prognosis in patients with peripheral pulmonary adenocarcinoma, the presence of which on CT images can remind us to provide patients with a more reasonable treatment. [ABSTRACT FROM AUTHOR]

Objective: Tertiary lymphoid structures (TLSs) are found in a variety of malignancies and affect the growth of tumors, but few studies have addressed their role in lung adenocarcinoma (LAC). We aimed to evaluate clinical features associated with TLSs in patients with LAC. Methods and Materials: A collection of resected pulmonary nodules in patients with LAC was retrospectively analyzed. TLSs were quantified by their number per square millimeter tumor area (density) and by the degree of lymphocyte aggregation (maturity) in each case. The correlation between TLS density and maturity and clinical features was calculated. Results: A total of 243 patients were selected, of whom 219 exhibited TLSs. The occurrence of TLSs was correlated with computed tomography (CT) features as follows: pure ground‐glass nodules (pGGNs) (n = 43) was associated with a lower occurrence rate than part‐solid nodules (PSNs) (n = 112) and solid nodules (SNs) were (n = 88) (p = 0.037). TLS density was correlated with age and CT features. Poisson regression showed higher TLS density in PSNs and SNs than in pGGNs (incidence rate ratio [IRR]: 3.137; 95% confidence interval [CI]: 1.35–7.27; p = 0.008 and IRR: 2.44; 95% CI: 1.02–5.85; p = 0.046, respectively). In addition, TLS density was higher in patients aged under 60 years than in those aged over 60 years (IRR: 0.605; 95% CI: 0.4–0.92; p = 0.018). The maturity of TLSs was higher in patients with higher tumor stages (p = 0.026). Conclusions: We demonstrated distinct profiles of TLSs in early LAC and their correlations with CT features, age, and tumor stages, which could help understand tumor progression and management. [ABSTRACT FROM AUTHOR]

Azoles were used as the primary antifungal agents to treat the Cryptococcus gattii infection. Evidence showed that subtypes of C. gattii respond differently to azoles, but the mechanism is largely elusive. In this study, we aimed to find the mechanisms of differences in azole drug susceptibility in different subtypes of C. gattii. Eight clinical strains of C. gattii were collected for molecular typing, multilocus sequence typing (MLST) analysis, and antifungal susceptibility testing. Based on drug susceptibility differences, the RNA sequencing data were analyzed to find candidate azole drug susceptibility genes, and qPCR validation was performed. Five VGI subtypes and three VGII subtypes were identified among the eight strains of C. gattii. The clinical isolates showed high genetic diversity, and seven sequence types (STs) were identified. The geometric mean (GM) of minimum inhibitory concentration (MIC) for fluconazole, voriconazole, and itraconazole of VGI subtype was significantly lower than that of VGII subtype, and genes related to transporter activities were differentially expressed between VGI and VGII strains. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs (differential expressed genes) were found to be enriched in multiple ABC transporters. We further performed qPCR to quantify the expression level of seven ABC transporters. We found that ABC transporters ATM1, MDR1, PDR5, PDR5-3 , and PXA2 were expressed significantly higher in VGII strains than in VGI strains. Our work revealed four novel ABC transporters, ATM1, PDR5, PDR5-3 , and PXA2 , promising candidate targets regulating azole susceptibility in C. gattii strains. Lay Summary Azoles were used as the primary antifungal agents for treating Cryptococuss gattii infection. Since subtypes of C. gattii respond differently to azoles. We analyzed mRNA expression profiles of different subtypes and identified four ABC transporters that could be potential genes regulating azole sensitivity. [ABSTRACT FROM AUTHOR]

Cryptococcus gattii (C. gattii) is a fungal pathogen that once caused an outbreak of cryptococcosis on Vancouver Island, and had spread worldwide, while few data were available in China. In this study, seven clinical isolates of C. gattii VGII were collected from 19 hospitals, Multi-locus Sequence Typing (MLST) analysis and whole-genome sequencing (WGS) was performed, combined with published data for phylogenetic analysis. In addition, in vitro antifungal susceptibility testing, phenotypic analysis, and in vivo virulence studies were performed, subsequently, histopathological analysis of lung tissue was performed. C.gattii VGII infected patients were mainly immunocompetent male, and most of them had symptoms of central nervous system (CNS) involvement. MLST results showed that isolates from China exhibited high genetic diversity, and sequence type (ST) 7 was the major ST among the isolates. Some clinical isolates showed a close phylogenetic relationship with strains from Australia and South America. All clinical isolates did not show resistance to antifungal drugs. In addition, there was no correlation between virulence factors (temperature, melanin production, and capsule size) and virulence while in vivo experiments showed significant differences in virulence among strains. Lung fungal burden and damage to lung tissue correlated with virulence, and degree of damage to lung tissue in mice may highlight differences in virulence. Our work seeks to provide useful data for molecular epidemiology, antifungal susceptibility, and virulence differences of C. gattii VGII in China. Author summary: Cryptococcus gattii is one of the life-threatening fungal pathogens that can infect immunocompetent individuals. C.gattii can be invaded through the respiratory tract and can be spread to the brain, causing meningoencephalitis and even death. In 1999, an outbreak of C. gattii VGII occurred on Vancouver Island in Canada and spread in the Pacific Northwest region, which attracted more attention. Compared with other nations, the data of C.gattii VGII in China was limited. To better understand the molecular epidemiology and microbiological characteristics of C.gattii VGII isolates from China, bioinformatics analysis and in vivo and in vitro experiments were performed for clinical strains. Multi-locus Sequence Typing and whole-genome sequencing reveal the genetic diversity of the isolates and genetic relationships with isolates from other countries. The antifungal drug susceptibility and virulence differences of the isolates were also investigated. The authors expect that our work can provide useful data for the prevention and control of C. gattii VGII in China and to draw more attention to C. gattii. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis.Methods: We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP.Results: CIP had an incidence of 4.7%, a median onset time of 10 weeks, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥ 3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥ 3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P < 0.05).Conclusion: Early-onset CIP cases were higher in the Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade and mainly presented with an OP-like radiographic pattern; whereas, late-onset CIP cases were lower in CTCAE grade and mainly presented with an NSIP-like radiographic pattern. Finally, the prognosis of the early-onset CIP group was poorer than that of the late-onset CIP group. We believe that this study will be helpful for clinicians for making early diagnosis and deciding treatment modalities for patients with CIP. [ABSTRACT FROM AUTHOR]

In this paper, we focus on the research of matching a computer-generated composite face sketch to a photograph. This is of great importance in the field of criminal investigation. To blend the different facial representation modalities, we propose a robust feature model by combining pixel-level features extracted from multi-scale key face patches and high-level features learned from a pre-trained deep learning-based model. At first, texture features are captured by a two-level histogram of oriented gradient descriptor, considering both the overall structure and local details. The semantic-level facial characteristics are analyzed through the high-level features of the Visual Geometry Group-Face (VGG-Face) network. Next, feature similarities between each sketch/photograph pair are measured by feature distance. Then, adaptive weights are assigned to each feature similarity, and score level fused according to their visual saliency contribution. Finally, the fused feature similarity is evaluated for matching purposes. After experimenting on the Pattern Recognition and Image Processing-Viewed Software-Generated Composite (PRIP-VSGC) database and the expanded University of Malta Composite Face Sketch (UoM-SGFS) database, it is found that this framework could achieve more satisfying results compared to the existing methods. [ABSTRACT FROM AUTHOR]

The dynamic phase transition properties for ferroelectric nanotube under a spin-1/2 transverse Ising model are studied under the effective field theory (EFT) with correlations. The temperature effects on the pseudo-spin systems are unveiled in three-dimensional (3-D) and two-dimensional (2-D) phase diagrams. Moreover, the dynamic behaviors of exchange interactions on the 3-D and 2-D phase transitions under high temperature are exhibited. The results present that it is hard to obtain pure ferroelectric phase under high temperature; that is, the vibration of orderly pseudo-spins cannot be eliminated completely. [ABSTRACT FROM AUTHOR]

Isoflurane, a widely used volatile anesthetic, induces neuronal apoptosis and memory impairments in various animal models. However, the potential mechanisms and effective pharmacologic agents are still not fully understood. The p38MAPK/ATF-2 pathway has been proved to regulate neuronal cell survival and inflammation. Besides, atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts neuroprotective effects. Thus, this study aimed to explore the influence of atorvastatin on isoflurane-induced neurodegeneration and underlying mechanisms. Aged C57BL/6 mice (20 months old) were exposed to isoflurane (1.5%) anesthesia for 6 h. Atorvastatin (5, 10, or 20 mg/kg body weight) was administered to the mice for 7 days. Atorvastatin attenuated the isoflurane-induced generation of ROS and apoptosis. Western blotting revealed a decrease in cleaved caspase-9 and caspase-3 expression in line with ROS levels. Furthermore, atorvastatin ameliorated the isoflurane-induced activation of p38MAPK/ATF-2 signaling. In a cellular study, we proved that isoflurane could induce oxidative stress and inflammation by activating the p38MAPK/ATF-2 pathway in BV-2 microglia cells. In addition, SB203580, a selected p38MAPK inhibitor, inhibited the isoflurane-induced inflammation, oxidative stress, and apoptosis. The results implied that p38MAPK/ATF-2 was a potential target for the treatment of postoperative cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background and Aims: Esophageal adenocarcinoma (EAC) patients usually have a poor prognosis without early diagnosis. In this study, we aimed to identify a novel signature to improve the prediction of overall survival (OS) in EAC. Methods: Eighty-one and 68 samples from The Cancer Genome Atlas (TCGA) and GSE19417 dataset were included for discovery and survival validation, respectively. In the TCGA cohort, a total of 1,811 DEmRNAs, 1,096 DElncRNAs, and 31 DEmiRNAs were identified between EAC and normal esophagus tissues. A mRNA–miRNA–lncRNA ceRNA network of EAC was established, which consisted of 94 DEmRNAs, 13 DEmiRNAs, and 46 DElncRNAs. Results: In this study, we identified eight genes (UBE2B, LAMP2, B3GNT2, TAF9B, EFNA1, PHF8, PIGA, and NEURL1) which were related to survival in EAC. The independent external microarray data from the Gene Expression Omnibus (GEO) was used to validate these candidate genes. The prognostic ability of the signature was also validated in EAC patients in our hospital. Patients assigned to the high-risk group had a poor overall survival rate compared with the low-risk. Conclusion: The current study provides novel insights into the mRNA-related ceRNA network in EAC and the eight mRNA biomarkers may be independent prognostic signatures in predicting the survival of EAC patients. [ABSTRACT FROM AUTHOR]

Background: Detailed catalog of lung cancer-associated gene mutations provides valuable information for lung cancer diagnosis and treatment. In China, there has never been a wide-ranging study cataloging lung cancer-associated gene mutations. This study aims to reveal a comprehensive catalog of lung cancer gene mutations in china, focusing on EGFR, ALK, KRAS, HER2, PIK3CA, MET, BRAF, HRAS, and CTNNB1 as major targets. Additionally, we also aim to correlate smoking history, gender, and age distribution and pathological types with various types of gene mutations. Patients and Methods: A retrospective data acquisition was conducted spanning 6 years (2013–2018) among all patients who underwent lung cancer surgeries not bronchial or percutaneous lung biopsy at three major tertiary hospitals. Finally, we identified 1,729 patients who matched our inclusion criteria. Results: 1081 patients (62.49%) harbored EGFR mutation. ALK (n = 42, 2.43%), KRAS (n = 201, 11.62%), CTNNB1 (n = 28, 1.62%), BRAF (n = 31, 1.79%), PIK3CA (n = 51, 2.95%), MET (n = 14, 0.81%), HER2 (n = 47, 2.72%), HRAS (n = 3, 0.17%), and other genes(n = 232, 13.4%). Females expressed 55.38% vs. males 44.62% mutations. Among subjects with known smoking histories, 32.82% smokers, 67.15% non-smokers were observed. Generally, 51.80% patients were above 60 years vs. 48.20% in younger patients. Pathological types found includes LUADs 71.11%, SQCCs 1.68%, ASC 0.75%, LCC 0.58%, SCC 0.35%, ACC 0.17%, and SC 0.06%, unclear 25.19%. Conclusion: We offer a detailed catalog of the distribution of lung cancer mutations. Showing how gender, smoking history, age, and pathological types are significantly related to the prevalence of lung cancer in China. [ABSTRACT FROM AUTHOR]

Direct quantification of exhausted T cells in human cancer is lacking, and its predictive value for checkpoint‐based treatment remains poorly investigated. We sought to systematically characterize the pan‐cancer landscape and molecular hallmarks of T‐cell dysfunction for the purpose of precision immunotherapy. Here, we defined a transcriptional signature for T‐cell exhaustion through analyzing differential gene expression between PD‐1‐high and PD‐1‐negative CD8+ T lymphocytes from primary non‐small cell lung cancer (NSCLC), followed by positive correlation tests with PDCD1 in TCGA lung carcinomas. A 78‐gene signature for exhausted CD8+ T cells (GET) was identified and validated to reflect dysfunctional immune state spanning different species and disease models. We discovered that GET estimation significantly correlated with intratumoral immune cytolytic activity (CYT) and T‐cell‐inflamed gene expression profile (GEP) across 30 solid tumor types. Miscellaneous tumor‐intrinsic and ‐extrinsic properties, in particular leukocyte proportions, genomic abnormalities, specific mutational signatures, and signaling pathways, were notably associated with GET levels. Furthermore, higher GET expression predicted an increased likelihood of clinical response to immune checkpoint inhibitors. These findings highlight the interrelation between T‐cell exhaustion and immune cytolytic activity at the pan‐cancer scale. The resulting inflamed tumor microenvironment may further crosstalk with other molecular and clinicopathological factors, which should be properly considered during immunotherapy biomarker development. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The manifestations of pulmonary cryptococcosis with multiple nodules or masses on computed tomography (CT) are diverse and difficult to differentiate from those of lung cancer and pulmonary tuberculosis. The present study compared the multislice spiral CT signs with pathological results and used the pathological results to explain the CT signs with the aim of improving the accuracy of the diagnosis of this disease. A retrospective analysis of 20 patients with primary pulmonary cryptococcosis with multiple nodules or masses was performed. Based on the CT signs, eight patients had been misdiagnosed with lung cancer accompanied by intrapulmonary metastasis andthree patients had been misdiagnosed with tuberculosis. The major CT manifestations were a cluster of nodules or masses located within 2 cm below the pleura and distributed along the bronchi. A total of nine patients had primary lesions with diameters of 1.1–2.0 cm and 12 patients had satellite lesions with diameters of 0.1–1.0 cm. Regarding treatment, 5 patients underwent surgical monotherapy, 12 patients underwent antifungal monotherapy and three patients received surgery in combination with antifungal therapy. HE staining indicated that Cryptococcus neoformans was engulfed by macrophages, which were surrounded by massive infiltrating lymphocytes and a large amount of fibrous tissue, which formed multinucleated macrophages or granulomas. Periodic acid-Schiff staining was positive and acid fast staining was negative. In conclusion, comparison of CT signs with the pathological manifestation of pulmonary cryptococcosis with multiple nodules or masses indicated that the pathological results may explain certain imaging signs. Combination of CT and pathological examination may provide a deeper understanding of this disease and improve the accuracy of its diagnosis. [ABSTRACT FROM AUTHOR]

With the rapid development of Internet technology, images on the Internet are used in various aspects of people’s lives. The security and authorization of images are strongly dependent on image quality. Some potential problems have also emerged, among which the quality assessment and denoising of images are particularly evident. This paper proposes a novel NR-IQA method based on the dual convolutional neural network structure, which combines saliency detection with the human visual system (HSV), used as a weighting function to reflect the important distortion caused by the local area. The model is trained using gray and color features in the HSV space. It is applied to the parameter selection of an image denoising algorithm. The experiment proves that our proposed method can accurately evaluate image quality in the process of denoising. It provides great help in parameter optimization iteration and improves the performance of the algorithm. Through experiments, we obtain both improved image quality and a reasonable result of subject assessment when the cascaded algorithm is applied in image security and authorization. [ABSTRACT FROM AUTHOR]

Thin-wall cystic lung cancer is uncommon. Consequently, there is a lack of knowledge concerning the features of this type of lung cancer, which may lead to misdiagnosis and delayed treatment. The aim of the present study is to understand the invasiveness and metastasis of thin-wall cystic lung cancer. The prognosis of this type of cancer will also be discussed. The present study attempted to determine the pathological interpretation of the imaging results. A total of 45 patients with this specific type of lung cancer were analyzed retrospectively based on the review of medical records, radiological findings, pathological changes and treatment strategies. Certain patients were also telephoned in order to learn about their recent physical conditions. Thin-wall cystic lung cancer displayed suspected malignant signs. The majority of these cases are adenocarcinoma, but certain cases of squamous cell carcinoma may also display cysts on their images. Although thin-wall cystic lung cancer is often thought to progress slowly, certain cases may progress rapidly. Distant metastasis, which is relatively rare, occurred in three cases. Cancer cells proliferate along the terminal bronchioles and destroy the lung tissues exposing the bronchial arteries and adjacent bronchi. Therefore, separation in cysts on the images was observed. In the majority of cases, the thin-wall cystic lung cancer proliferates slowly, but in a few cases it may be very aggressive. [ABSTRACT FROM AUTHOR]

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS. [ABSTRACT FROM AUTHOR]

Linqi Wang should be listed as the ninth author and affiliated with State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Correction: Molecular epidemiology and microbiological characteristics of Cryptococcus gattii VGII isolates from China Linqi Wang is not included in the author byline. [Extracted from the article]

The microenvironment encompassing a variety of non-malignant cells in close proximity with malignant tumor cells has been well known to significantly affect the behavior of tumor cells. In this study, we therefore studied the mechanism of bone marrow stromal cells in protection of lymphoma cells from spontaneous apoptosis. We demonstrated that adhesion of the freshly isolated lymphoma B cells to bone marrow stromal cells or freshly isolated lymphoma stromal cells inhibited B cell spontaneous apoptosis in culture. This inhibition of apoptosis correlated with decreased cleavage of caspase-3/8 and increased activation of canonical and non-canonical NF-κB signaling pathway. In addition to BAFF signaling which has been reported as a functional determinant for B lymphoma cell survival in the bone marrow environment, we demonstrated RANKL from BMSCs works synergistically with BAFF to activate NF-κB signaling pathway and thus protects lymphoma B cells from spontaneous apoptosis. [ABSTRACT FROM AUTHOR]

A new class of multifunctional nanobubble using poly(lactic-co-glycolic acid) (PLGA) has been developed as ultrasound imaging contrast agents, doxorubicin carriers, and enhancers of ultrasound-mediated drug delivery. The doxorubicin nanobubble (DOX-NB) wrapping carbon tetrafluoride gas was prepared with double emulsion method. We evaluated the enhanced ultrasonic function of the DOX-NB in vivo; its antitumor function was confirmed. The diameter of the prepared bubble was 500 nm, and the potential was −23 mV. The drug loading and encapsulation efficiency of the bubble were 78.6 and 7.4 %, respectively. Therefore, the DOX-NB greatly enhanced ultrasound imaging in vivo. Ultrasound combined with DOX-NB had significant antitumor effect. Compared with other groups, the tumor growth rate and the proliferation index were the lowest while the survival rate and apoptosis index were the highest. [ABSTRACT FROM AUTHOR]

A post-transcriptional pathway by which TGF-β modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-β for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-β induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-β treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-β-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma. [ABSTRACT FROM AUTHOR]

Granulosa cells (GCs) are essential for proper oocyte, follicular development, and steroidogenesis in the ovary. Transforming growth factor β (TGF-β) superfamily members are critical in regulating GCs growth and differentiation. Smad3 is known to serve as a signaling intermediate for the TGF-β; however, the functions of Smad3 in the human GCs remain unidentified. In this study, the luteinized GCs collected from follicular aspirates from patients undergoing in vitro fertilization were cultured and engineered to overexpress and knockdown Smad3, which were validated by RT-PCR and Western blotting. Immunocytochemistry showed that Smad3 protein was strongly expressed in human ovarian luteinized GCs. EdU incorporation demonstrated that Smad3 promoted the proliferation of GCs, and the expression of PCNA was also enhanced by Smad3. ELISA analysis indicated that the secretion of both estradiol and progesterone was stimulated by Smad3. In addition, Smad3 upregulated the level of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), and protein kinase A (PKA) proteins. We subsequently added special PKA inhibitor H89 into the GCs and found that the stimulating effect on the growth of GCs by Smad3 was blocked partly. The morphology of cultured GCs was changed by Smad3, and the expression level of integrin β1 was enhanced by Smad3. Kindlin-2, an important cellular mediating molecule of integrin β signaling, was expressed in human ovarian luteinized GCs and was upregulated by Smad3. Our results indicated that Smad3 promoted the proliferation and steroidogenesis of human ovarian luteinized GCs, and these effects may be mediated by the FSHR/LHR-PKA signaling pathway. © 2014 IUBMB Life, 66(6):424-437, 2014 [ABSTRACT FROM AUTHOR]

A modified generalized Morse (mGM) equation of state (EOS) is proposed that can incorporate the cohesive energy data correctly. It is compared with a four-parameter modified Rose EOS (MR EOS) which is proposed by following the Rose's approach and the Vinet EOS. The MR, mGM and Vinet EOSs are applied to five transition metals to fit all experimental compression data available. The results show that for all pressure ranges the mGM EOS gives the best fitting results. From the comparison of variation of pressure and energy versus compression ratio between MR and mGM EOS, it is clear that the pressure and energy of the MR EOS oscillate both in the neighborhood of (V/V0) ≈ 0.005 and in the range (V/V0) > 1. Such oscillations are physically incorrect, and the tendency of the mGM EOS are physically correct both in the neighborhood of (V/V0) ≈ 0.005 and in the range (V/V0) > 1. Generally speaking, the mGM EOS has evident advantage among the three EOSs, and the MR EOS's practical applications are seriously limited because of the physically incorrect oscillations. [ABSTRACT FROM AUTHOR]

The analytic mean-field approach (AMFP) was applied to study the thermodynamic properties of Zirconium (Zr). The analytic expressions for the Helmholtz free energy, internal energy and equation of state have been derived. The formalism for the case of the Morse potential is used in this work. The four potential parameters are determined by fitting the molar volume of the three phases of Zr. The calculated molar volume of α, β and ω Zr are in fairly good agreement with the available experimental data. The results presented in this paper verify that the AMFP is a useful approach to study the thermodynamic properties of Zr. Furthermore, we predict the variation of the relationship of free energy and internal energy versus the molar volume at various temperatures and the dependence of the bulk modulus, the thermal expansion coefficient and the heat capacity on temperature at zero pressure of α, β and ω Zr. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most life-threatening malignancies worldwide. Despite advances in checkpoint immunotherapy for patients with cancer, the current immunotherapies have demonstrated limited benefits for the treatment of pancreatic cancer. Apart from the intricate microenvironments that restrict T-cell function, membrane proteins other than programmed death-ligand 1 may also facilitate immune escape of tumor cells. The present study investigated the membrane proteins of seven paired pancreatic adenocarcinoma (PAAD) and adjacent normal tissues with mass spectrometry, and identified 10 up-and eight downregulated membrane proteins in PAAD. Together with the online database analysis, the results showed that the CASK protein was upregulated in PAAD samples and cell lines, and predicts poor outcomes in patients with PAAD. Furthermore, the results exhibited downregulated CD36 and EPB42 in PAAD samples and cell lines, and higher levels of CD36. EPB42 was shown to predict improved survival outcomes in patients with PAAD. Overall, the results of the present study revealed PAAD-specific membrane proteins as potential diagnostic markers and drug-targets for the immunotherapy of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Immune-related adverse events (irAEs), caused by anti-PD-1/PD-L1 antibodies, can lead to fulminant and even fatal consequences and thus require early detection and aggressive management. However, a comprehensive approach to identify biomarkers of irAE is lacking. Here, we utilize a strategy that combines pharmacovigilance data and omics data, and evaluate associations between multi-omics factors and irAE reporting odds ratio across different cancer types. We identify a bivariate regression model of LCP1 and ADPGK that can accurately predict irAE. We further validate LCP1 and ADPGK as biomarkers in an independent patient-level cohort. Our approach provides a method for identifying potential biomarkers of irAE in cancer immunotherapy using both pharmacovigilance data and multi-omics data. Immunotherapy, the reactivation of the immune system to recognize cancer cells, can be accompanied by severe adverse effects. Here, the authors use pharmacovigilance and genomic data to be able to predict which patients might be susceptible to such severe events. [ABSTRACT FROM AUTHOR]

Due to its negligible solubility, it is difficult to obtain a W-30Cu composite with a homogenous microstructure. However, with a selected W skeleton, a homogeneous phase distribution was achieved for a W-30Cu composite in the present study. By detailed characterization of the mechanical performance and microstructure of the W-30Cu composite, as well as the stress distribution state under a loading condition, the effects of microstructure homogeneity on the mechanical properties and failure mechanisms are identified. The mechanisms by which the ductility and strength depend on microstructure homogeneity contain the effects on plastic deformation and stress coordination of the Cu phase network. The dominant factors for the high ductility and strength of W-30Cu composites are proposed. [ABSTRACT FROM AUTHOR]