Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.

BACKGROUND: Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant ataxia with invariable sensory neuropathy originally described in a family with Swedish ancestry residing in Utah more than 25 years ago. Despite tight linkage to the 16q22 region, the molecular diagnosis has since remained elusive. OBJECTIVES: Inspired by pathogenic structural variation implicated in other 16q-ataxias with linkage to the same locus, we revisited the index SCA4 cases from the Utah family using novel technologies to investigate structural variation within the candidate region. METHODS: We adopted a targeted long-read sequencing approach with adaptive sampling on the Oxford Nanopore Technologies (ONT) platform that enables the detection of segregating structural variants within a genomic region without a priori assumptions about any variant features. RESULTS: Using this approach, we found a heterozygous (GGC)n repeat expansion in the last coding exon of the zinc finger homeobox 3 (ZFHX3) gene that segregates with disease, ranging between 48 and 57 GGC repeats in affected probands. This finding was replicated in a separate family with SCA4. Furthermore, the estimation of this GGC repeat size in short-read whole genome sequencing (WGS) data of 21,836 individuals recruited to the 100,000 Genomes Project in the UK and our in-house dataset of 11,258 exomes did not reveal any pathogenic repeats, indicating that the variant is ultrarare. CONCLUSIONS: These findings support the utility of adaptive long-read sequencing as a powerful tool to decipher causative structural variation in unsolved cases of inherited neurological disease. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The value of calcofluor white in the diagnosis of invasive fungal diseases.

PURPOSE: To evaluate the value of calcofluor white in the diagnosis of invasive fungal disease (IFD). METHODS: A total of 84 patients with possible pulmonary fungal infection who underwent bronchoscopy with bronchoalveolar lavage fluid (BALF) were included. All BALF specimens were subjected to Calcofluor white (CFW), potassium hydroxide (KOH) and Gram stains. RESULTS: CFW has the most sensitivity than KOH and Gram staining. The specificity of CFW was 92.00 %, which was lower than that of Gram staining. The PPVs for CFW, KOH and Gram staining were 94.44 %, 84.62 % and 80.00 % respectively. The NPVs for CFW, KOH and Gram staining was 47.92 %, 32.39 % and 30.38 % respectively. The AUCs of these three methods were 0.748, 0.550 and 0.510 respectively. CONCLUSION: CFW is superior to KOH and Gram staining in the diagnosis of invasive fungal diseases.

Genetic topography and cortical cell loss in Huntington's disease link development and neurodegeneration.

Cortical cell loss is a core feature of Huntington's disease (HD), beginning many years before clinical motor diagnosis, during the premanifest stage. However, it is unclear how genetic topography relates to cortical cell loss. Here, we explore the biological processes and cell types underlying this relationship and validate these using cell-specific post-mortem data. Eighty premanifest participants on average 15 years from disease onset and 71 controls were included. Using volumetric and diffusion MRI we extracted HD-specific whole brain maps where lower grey matter volume and higher grey matter mean diffusivity, relative to controls, were used as proxies of cortical cell loss. These maps were combined with gene expression data from the Allen Human Brain Atlas (AHBA) to investigate the biological processes relating genetic topography and cortical cell loss. Cortical cell loss was positively correlated with the expression of developmental genes (i.e. higher expression correlated with greater atrophy and increased diffusivity) and negatively correlated with the expression of synaptic and metabolic genes that have been implicated in neurodegeneration. These findings were consistent for diffusion MRI and volumetric HD-specific brain maps. As wild-type huntingtin is known to play a role in neurodevelopment, we explored the association between wild-type huntingtin (HTT) expression and developmental gene expression across the AHBA. Co-expression network analyses in 134 human brains free of neurodegenerative disorders were also performed. HTT expression was correlated with the expression of genes involved in neurodevelopment while co-expression network analyses also revealed that HTT expression was associated with developmental biological processes. Expression weighted cell-type enrichment (EWCE) analyses were used to explore which specific cell types were associated with HD cortical cell loss and these associations were validated using cell specific single nucleus RNAseq (snRNAseq) data from post-mortem HD brains. The developmental transcriptomic profile of cortical cell loss in preHD was enriched in astrocytes and endothelial cells, while the neurodegenerative transcriptomic profile was enriched for neuronal and microglial cells. Astrocyte-specific genes differentially expressed in HD post-mortem brains relative to controls using snRNAseq were enriched in the developmental transcriptomic profile, while neuronal and microglial-specific genes were enriched in the neurodegenerative transcriptomic profile. Our findings suggest that cortical cell loss in preHD may arise from dual pathological processes, emerging as a consequence of neurodevelopmental changes, at the beginning of life, followed by neurodegeneration in adulthood, targeting areas with reduced expression of synaptic and metabolic genes. These events result in age-related cell death across multiple brain cell types.

aws-s3-integrity-check: an open-source bash tool to verify the integrity of a dataset stored on Amazon S3.

Amazon Simple Storage Service (Amazon S3) is a widely used platform for storing large biomedical datasets. Unintended data alterations can occur during data writing and transmission, altering the original content and generating unexpected results. However, no open-source and easy-to-use tool exists to verify end-to-end data integrity. Here, we present aws-s3-integrity-check, a user-friendly, lightweight, and reliable bash tool to verify the integrity of a dataset stored in an Amazon S3 bucket. Using this tool, we only needed ∼114 min to verify the integrity of 1,045 records ranging between 5 bytes and 10 gigabytes and occupying ∼935 gigabytes of the Amazon S3 cloud. Our aws-s3-integrity-check tool also provides file-by-file on-screen and log-file-based information about the status of each integrity check. To our knowledge, this tool is the only open-source one that allows verifying the integrity of a dataset uploaded to the Amazon S3 Storage quickly, reliably, and efficiently. The tool is freely available for download and use at https://github.com/SoniaRuiz/aws-s3-integrity-check and https://hub.docker.com/r/soniaruiz/aws-s3-integrity-check.

Clinical diagnostic value of serum soluble IL-2 receptor for stage I sarcoidosis in benign isolated mediastinal and hilar lymphadenopathy.

BACKGROUND: Serum soluble interleukin-2 receptor (sIL-2R) is recognized as a marker of T-cell activation and is abnormally elevated in sarcoidosis. However, its value for stage I sarcoidosis in benign granulomatous diseases is unclear. METHODS: We enrolled 33 stage I sarcoidosis patients, 17 lymph node tuberculosis patients, 15 reactive lymphadenopathy patients, and 11 healthy controls. Serum biomarkers concentrations were collected and collated. RESULTS: Serum sIL-2R concentrations were the highest in stage I sarcoidosis. The AUC of serum sIL-2R for stage I sarcoidosis was 0.7452 in all subjects and 0.6861 in granulomatous diseases. The AUCs of two combined diagnostic forms, sIL-2R with angiotensin-converting enzyme (ACE) and sIL-2R with ACE, erythrocyte sedimentation rate (ESR), and lactate dehydrogenase (LDH) were 0.7994 and 0.891 in all subjects, respectively. In granulomatous disease groups for ROC analysis, the best cut-off value of sIL-2R was 745.00 U/ml with 48.50% sensitivity and 84.40% specificity. The combination of four parameters increased the diagnostic accuracy for stage I sarcoidosis in granulomatous diseases (74.10% sensitivity and 100% specificity). Serum sIL-2R concentrations were positively correlated with serum ACE (r = 0.4652, P = 0.0126). CONCLUSION: Serum sIL-2R appeared to be valuable in identifying stage I sarcoidosis in a group of benign granulomatous disorders.

The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases.

Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how common variants associated with neurodegenerative disease risk are maintained by natural selection in the population despite their deleterious effects. In this study, we aimed to quantify the genome-wide contribution of Neanderthal introgression and positive selection to the heritability of complex neurodegenerative disorders to address these questions. We used stratified-linkage disequilibrium score regression to investigate the relationship between five SNP-based signatures of natural selection, reflecting different timepoints of evolution, and genome-wide associated variants of the three most prevalent neurodegenerative disorders: Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease. We found no evidence for enrichment of positively-selected SNPs in the heritability of Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, suggesting that common deleterious disease variants are unlikely to be maintained by positive selection. There was no enrichment of Neanderthal introgression in the SNP-heritability of these disorders, suggesting that Neanderthal admixture is unlikely to have contributed to disease risk. These findings provide insight into the origins of neurodegenerative disorders within the evolution of Homo sapiens and addresses a long-standing debate, showing that Neanderthal admixture is unlikely to have contributed to common genetic risk of neurodegeneration in anatomically-modern humans.

Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer.

The present study sought to investigate the correlation between CAAP1 and platinum resistance in ovarian cancer and to preliminarily explore the potential biological function of CAAP1. Proteomic analysis was used to analyze differentially expressed proteins in platinum-sensitive and -resistant tissue samples of ovarian cancer. The Kaplan-Meier plotter was used for prognostic analysis. Immunohistochemistry assay and chi-square test were employed to explore the relationship between CAAP1 and platinum resistance in tissue samples. Lentivirus transfection, immunoprecipitation-mass spectrometry, and bioinformatics analysis were used to determine the potential biological function of CAAP1. Based on results, the expression level of CAAP1 was significantly higher in platinum-sensitive tissues compared to that in resistant tissues. Chi-square test demonstrated that there is a negative correlation between high expression of CAAP1 and platinum resistance. Overexpression of CAAP1 increased cis­platinum sensitivity of the A2780/DDP cell line likely via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. In summary, there is a negative correlation between high expression of CAAP1 and platinum resistance. CAAP1 might be a potential biomarker for platinum resistance in ovarian cancer. SIGNIFICANCE: Platinum resistance is a key factor affecting the survival of ovarian cancer patients. Understanding the mechanisms of platinum resistance is highly important for ovarian cancer management. Here, we performed the DIA- and DDA-based proteomics to analyze differentially expressed proteins in tissue and cell samples of ovarian cancer. We found that the protein identified as CAAP1, which was first reported to be involved in the regulation of apoptosis, may be negatively correlates with platinum resistance in ovarian cancer. In addition, we also found that CAAP1 enhanced the sensitivity of platinum-resistant cells to cis­platinum via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. Our data would be useful to reveal novel molecular mechanisms of platinum resistance in ovarian cancer.

Diagnostic performance of cryobiopsy guided by radial-probe EBUS with a guide sheath for peripheral pulmonary lesions.

OBJECTIVE: Transbronchial lung cryobiopsy (TBCB) has developed rapidly and has become one of the research hotspots of lung biopsy technology. The present study sought to evaluate the efficacy of TBCB guided by radial-probe EBUS (RP-EBUS) and a guide sheath (GS) without fluoroscopy for peripheral pulmonary lesions. METHODS: In this retrospective study, McNemar's test was used in order to compare TBCB and transbronchial forceps biopsy (TBFB) in terms of diagnostic performance. A multivariate logistic regression model was designed to explore the association between predictive variables and the diagnostic yield of TBCB. RESULTS: A total of 168 patients underwent GS-guided RP-EBUS. Of those, 157 had lesions that were visible and 11 had lesions that were not. Of those 157 patients, 24 were excluded because of missing data or an unclear final diagnosis. Therefore, 133 patients underwent RP-EBUS-GS-guided TBFB and TBCB. The pooled diagnostic yield of RP-EBUS-GS-guided TBCB without fluoroscopy was 71.5% (103/144). In 133 patients, the diagnostic yield of TBCB was significantly higher than that of TBFB (77.4% vs. 59.4%; p < 0.05). Multivariate analysis indicated that lesion size and site were independently associated with the diagnostic yield of TBCB (OR = 2.8, p = 0.03 and OR = 4.1, p = 0.01, respectively), although cryoprobe size was not. There was no significant difference between the 1.1-mm cryoprobe and the 1.9-mm cryoprobe in terms of diagnostic performance (78.4% vs. 76.8%; p > 0.05). CONCLUSIONS: GS-guided RP-EBUS is regarded as a practical option for guiding cryobiopsy, although it may not be able to replace fluoroscopy. Peripheral pulmonary lesions not located in the upper lobes or larger than 30 mm are significantly associated with a higher diagnostic yield of cryobiopsy.

Functional genomics provide key insights to improve the diagnostic yield of hereditary ataxia.

Improvements in functional genomic annotation have led to a critical mass of neurogenetic discoveries. This is exemplified in hereditary ataxia, a heterogeneous group of disorders characterised by incoordination from cerebellar dysfunction. Associated pathogenic variants in more than 300 genes have been described, leading to a detailed genetic classification partitioned by age-of-onset. Despite these advances, up to 75% of patients with ataxia remain molecularly undiagnosed even following whole genome sequencing, as exemplified in the 100 000 Genomes Project. This study aimed to understand whether we can improve our knowledge of the genetic architecture of hereditary ataxia by leveraging functional genomic annotations, and as a result, generate insights and strategies that raise the diagnostic yield. To achieve these aims, we used publicly-available multi-omics data to generate 294 genic features, capturing information relating to a gene's structure, genetic variation, tissue-specific, cell-type-specific and temporal expression, as well as protein products of a gene. We studied these features across genes typically causing childhood-onset, adult-onset or both types of disease first individually, then collectively. This led to the generation of testable hypotheses which we investigated using whole genome sequencing data from up to 2182 individuals presenting with ataxia and 6658 non-neurological probands recruited in the 100 000 Genomes Project. Using this approach, we demonstrated a high short tandem repeat (STR) density within childhood-onset genes suggesting that we may be missing pathogenic repeat expansions within this cohort. This was verified in both childhood- and adult-onset ataxia patients from the 100 000 Genomes Project who were unexpectedly found to have a trend for higher repeat sizes even at naturally-occurring STRs within known ataxia genes, implying a role for STRs in pathogenesis. Using unsupervised analysis, we found significant similarities in genomic annotation across the gene panels, which suggested adult- and childhood-onset patients should be screened using a common diagnostic gene set. We tested this within the 100 000 Genomes Project by assessing the burden of pathogenic variants among childhood-onset genes in adult-onset patients and vice versa. This demonstrated a significantly higher burden of rare, potentially pathogenic variants in conventional childhood-onset genes among individuals with adult-onset ataxia. Our analysis has implications for the current clinical practice in genetic testing for hereditary ataxia. We suggest that the diagnostic rate for hereditary ataxia could be increased by removing the age-of-onset partition, and through a modified screening for repeat expansions in naturally-occurring STRs within known ataxia-associated genes, in effect treating these regions as candidate pathogenic loci.

Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia.

BACKGROUND: The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis. METHODS: We sequenced the genomes of six persons with autosomal dominant LOCA who were members of three French Canadian families and identified a candidate pathogenic repeat expansion. We then tested for association between the repeat expansion and disease in two independent case-control series - one French Canadian (66 patients and 209 controls) and the other German (228 patients and 199 controls). We also genotyped the repeat in 20 Australian and 31 Indian index patients. We assayed gene and protein expression in two postmortem cerebellum specimens and two induced pluripotent stem-cell (iPSC)-derived motor-neuron cell lines. RESULTS: In the six French Canadian patients, we identified a GAA repeat expansion deep in the first intron of FGF14, which encodes fibroblast growth factor 14. Cosegregation of the repeat expansion with disease in the families supported a pathogenic threshold of at least 250 GAA repeats ([GAA]≥250). There was significant association between FGF14 (GAA)≥250 expansions and LOCA in the French Canadian series (odds ratio, 105.60; 95% confidence interval [CI], 31.09 to 334.20; P<0.001) and in the German series (odds ratio, 8.76; 95% CI, 3.45 to 20.84; P<0.001). The repeat expansion was present in 61%, 18%, 15%, and 10% of French Canadian, German, Australian, and Indian index patients, respectively. In total, we identified 128 patients with LOCA who carried an FGF14 (GAA)≥250 expansion. Postmortem cerebellum specimens and iPSC-derived motor neurons from patients showed reduced expression of FGF14 RNA and protein. CONCLUSIONS: A dominantly inherited deep intronic GAA repeat expansion in FGF14 was found to be associated with LOCA. (Funded by Fondation Groupe Monaco and others.).

IntroVerse: a comprehensive database of introns across human tissues.

Dysregulation of RNA splicing contributes to both rare and complex diseases. RNA-sequencing data from human tissues has shown that this process can be inaccurate, resulting in the presence of novel introns detected at low frequency across samples and within an individual. To enable the full spectrum of intron use to be explored, we have developed IntroVerse, which offers an extensive catalogue on the splicing of 332,571 annotated introns and a linked set of 4,679,474 novel junctions covering 32,669 different genes. This dataset has been generated through the analysis of 17,510 human control RNA samples from 54 tissues provided by the Genotype-Tissue Expression Consortium. IntroVerse has two unique features: (i) it provides a complete catalogue of novel junctions and (ii) each novel junction has been assigned to a specific annotated intron. This unique, hierarchical structure offers multiple uses, including the identification of novel transcripts from known genes and their tissue-specific usage, and the assessment of background splicing noise for introns thought to be mis-spliced in disease states. IntroVerse provides a user-friendly web interface and is freely available at https://rytenlab.com/browser/app/introverse.

Diagnostic performance of cryobiopsy guided by radial-probe EBUS with a guide sheath for peripheral pulmonary lesions / Desempenho diagnóstico da criobiópsia guiada por EBUS radial com bainha guia para lesões pulmonares periféricas

ABSTRACT Objective: Transbronchial lung cryobiopsy (TBCB) has developed rapidly and has become one of the research hotspots of lung biopsy technology. The present study sought to evaluate the efficacy of TBCB guided by radial-probe EBUS (RP-EBUS) and a guide sheath (GS) without fluoroscopy for peripheral pulmonary lesions. Methods: In this retrospective study, McNemar's test was used in order to compare TBCB and transbronchial forceps biopsy (TBFB) in terms of diagnostic performance. A multivariate logistic regression model was designed to explore the association between predictive variables and the diagnostic yield of TBCB. Results: A total of 168 patients underwent GS-guided RP-EBUS. Of those, 157 had lesions that were visible and 11 had lesions that were not. Of those 157 patients, 24 were excluded because of missing data or an unclear final diagnosis. Therefore, 133 patients underwent RP-EBUS-GS-guided TBFB and TBCB. The pooled diagnostic yield of RP-EBUS-GS-guided TBCB without fluoroscopy was 71.5% (103/144). In 133 patients, the diagnostic yield of TBCB was significantly higher than that of TBFB (77.4% vs. 59.4%; p < 0.05). Multivariate analysis indicated that lesion size and site were independently associated with the diagnostic yield of TBCB (OR = 2.8, p = 0.03 and OR = 4.1, p = 0.01, respectively), although cryoprobe size was not. There was no significant difference between the 1.1-mm cryoprobe and the 1.9-mm cryoprobe in terms of diagnostic performance (78.4% vs. 76.8%; p > 0.05). Conclusions: GS-guided RP-EBUS is regarded as a practical option for guiding cryobiopsy, although it may not be able to replace fluoroscopy. Peripheral pulmonary lesions not located in the upper lobes or larger than 30 mm are significantly associated with a higher diagnostic yield of cryobiopsy.

RESUMO Objetivo: A criobiópsia transbrônquica (CBTB) desenvolveu-se rapidamente e tornou-se um dos focos de pesquisa de tecnologia de biópsia pulmonar. O presente estudo buscou avaliar a eficácia da CBTB guiada por EBUS radial com bainha guia sem fluoroscopia no diagnóstico de lesões pulmonares periféricas. Métodos: Neste estudo retrospectivo, o teste de McNemar foi usado para comparar a CBTB e a biópsia transbrônquica com pinça (BTB) quanto ao desempenho diagnóstico. Um modelo de regressão logística multivariada foi criado para explorar a relação entre variáveis preditivas e o rendimento diagnóstico da CBTB. Resultados: Um total de 168 pacientes foram submetidos a EBUS radial com bainha guia. Destes, 157 apresentavam lesões que puderam ser visualizadas e 11 apresentavam lesões que não puderam ser visualizadas. Dos 157 pacientes, 24 foram excluídos em virtude de dados incompletos ou diagnóstico final incerto. Portanto, 133 pacientes foram submetidos a BTB e CBTB guiadas por EBUS radial com bainha guia. O rendimento diagnóstico combinado da CBTB guiada por EBUS radial com bainha guia foi de 71,5%. O rendimento diagnóstico da CBTB foi significativamente maior que o da BTB (77,4% vs. 59,4%; p < 0,05). A análise multivariada indicou que o tamanho e o local da lesão apresentaram relação independente com o rendimento diagnóstico da CBTB (OR = 2,8, p = 0,03 e OR = 4,1, p = 0,01, respectivamente); o tamanho da criossonda, por sua vez, não apresentou relação com o rendimento diagnóstico da CBTB. Não houve diferença significativa entre a criossonda de 1,1 mm e a de 1,9 mm no que tange ao desempenho diagnóstico (78,4% vs. 76,8%; p > 0,05). Conclusões: EBUS radial com bainha guia é uma opção prática para guiar a criobiópsia, embora talvez não possa substituir a fluoroscopia. Lesões pulmonares periféricas que não estejam nos lobos superiores ou que tenham mais de 30 mm apresentam relação significativa com maior rendimento diagnóstico da criobiópsia.

Advice for smokers in smoking cessation clinic: a review.

Background: Tobacco dependence has become a global public health concern. We chose to investigate the modifiable factors and motivations during the period of smoking cessation based on the mechanism of nicotine addiction. Methods: We selected emotion, sleep, alcohol, caffeine beverages, mental activities after dinner, exercise and CYP2A6 genotype as influencing factors, and provided corresponding recommendations for smokers based on these factors. Based on these characteristics, we reviewed literature and summarized the relationship between these factors and nicotine dependence or smoking. Results: Different emotion, sleep deficiency, caffeine intake, alcohol consumption, mental activities after dinner, physical exercises and CYP2A6 genotype have an effect on daily smoking and nicotine dependence. Conclusion: These suggestions related literature-derived factors may increase the success rate of smoking cessation.

An Innovative Method: Predicting the Visibility of Radial Endobronchial Ultrasound for Peripheral Pulmonary Nodules by Virtual Bronchoscopic Navigation.

Background: The diagnosis of peripheral pulmonary nodules (PPNs) still is the key and difficult point. Previous studies have demonstrated that the diagnostic yield of radial endobronchial ultrasound (rEBUS) visible nodules is significantly higher than that of invisible nodules. The traditional method of predicting the rEBUS-visibility of nodules is based on the CT-bronchus signs, but its effectiveness may be unsatisfactory. Objective: We innovate a valuable predictive model based on virtual bronchoscopic navigation to identify beforehand which PPNs are likely to be successfully visualized by rEBUS. The innovative predictor is the ratio of the size of lesions (S) to the shortest straight-line distance (D) from the terminal point of the virtual navigation path to the localization point of the nodule. Methods: This is a retrospective study. On the training dataset of 214 patients, a receiver operating characteristic curve was drawn to understand the utility of the predictive model and get the optimal cut-off points. Ninety-two cases were enrolled in the validation dataset to validate the external predictive accuracy of the predictor. Results: The optimal cut-off point of the curve was 1.84 with the Youden index of 0.65, at which point the area under the curve was 0.85 (95% CI: 0.76-0.95). The predictor has a good performance in the validation dataset with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 81%, 100%, 100%, 71%, and 87%, respectively. Conclusion: The S/D ratio is a valuable and innovative method to identify beforehand which PPNs are likely to be successfully visualized by rEBUS. If the S/D ratio of the nodule is greater than 1.84, it will be visualized by rEBUS.

PhenoExam: gene set analyses through integration of different phenotype databases.

BACKGROUND: Gene set enrichment analysis (detecting phenotypic terms that emerge as significant in a set of genes) plays an important role in bioinformatics focused on diseases of genetic basis. To facilitate phenotype-oriented gene set analysis, we developed PhenoExam, a freely available R package for tool developers and a web interface for users, which performs: (1) phenotype and disease enrichment analysis on a gene set; (2) measures statistically significant phenotype similarities between gene sets and (3) detects significant differential phenotypes or disease terms across different databases. RESULTS: PhenoExam generates sensitive and accurate phenotype enrichment analyses. It is also effective in segregating gene sets or Mendelian diseases with very similar phenotypes. We tested the tool with two similar diseases (Parkinson and dystonia), to show phenotype-level similarities but also potentially interesting differences. Moreover, we used PhenoExam to validate computationally predicted new genes potentially associated with epilepsy. CONCLUSIONS: We developed PhenoExam, a freely available R package and Web application, which performs phenotype enrichment and disease enrichment analysis on gene set G, measures statistically significant phenotype similarities between pairs of gene sets G and G' and detects statistically significant exclusive phenotypes or disease terms, across different databases. We proved with simulations and real cases that it is useful to distinguish between gene sets or diseases with very similar phenotypes. Github R package URL is https://github.com/alexcis95/PhenoExam . Shiny App URL is https://alejandrocisterna.shinyapps.io/phenoexamweb/ .

Study on the effects of combined tea drinking and mental activity after dinner on smokers in China.

INTRODUCTION: Cigarette and tobacco use is a leading cause of chronic obstructive pulmonary disease, lung cancer, and other malignant tumors. In China, people prefer to engage in mental activities (gambling, overtime work, playing video games, or other mental activities) on the weekends or during spare time, especially in the evening before they prepare for bed. In China, smokers frequently consume tea while smoking. The relationship between smokers who consume tea, engage in mental activities after dinner, or both (drinking tea and engaging in cognitive activities after dinner together), and daily cigarette smoking or nicotine addiction must be clarified. METHODS: A total of 438 smokers were included in the study. Age, gender, body mass index (BMI), smoking habits, Fagerström test for nicotine dependence scores, and behaviors, were recorded. The study excluded smokers with a Fagerström score <1 or with a mental disorder diagnosis. The smokers were divided into four groups based on their behaviors: those who did not drink tea, did not engage in mental activities after dinner, those who drank tea only, those who engaged in mental activities only, and those who engaged in both. RESULTS: Only drinking tea or doing mental activities after dinner cannot increase cigarettes per day (22.20 ± 10.143 vs 23.49 ± 11.966, p=0.362; 22.20 ± 10.143 vs 22.66 ± 1.192, p=0.750) or FTND scores [6.0 (4.0; 7.0) vs 6.0 (4.0; 7.75), p=0.941; 6.0 (4.0; 7.0) vs 6.0 (4.25; 7.75), p=0.980]. People who drink tea and engage in mental activities after dinner smoke more (22.20 ± 10.143 vs 30.75 ± 17.264, p<0.0001) and have higher nicotine dependence levels [6.0 (4.0; 7.0) vs 7.0 (5.0; 8.0), p=0.015]. CONCLUSIONS: The consumption of tea or a mental activity after dinner is not associated with daily smoking or nicotine dependence. There is an association between the combined behaviors (tea drinking and mental activity after dinner) and the daily consumption of cigarettes, and the degree of nicotine dependence.

Modified Intraperitoneal Chemotherapy Without Bevacizumab as a First-Line Therapy for Newly Diagnosed Advanced Epithelial Ovarian Cancer-Two Centers Experiences.

Objectives: To evaluate whether the modified intraperitoneal plus intravenous chemotherapy regimen as a first-line therapy for advanced epithelial ovarian cancer (EOC) in China can be well-tolerated or confer any potential benefit on survival. Methods: We evaluated the outcomes of women with newly diagnosed advanced-stage III-IV EOC treated with optimal cytoreductive surgery (<1 cm) and subsequent intraperitoneal plus intravenous chemotherapy or intravenous chemotherapy from January 2005 to December 2017 at two Gynecologic Oncology Centers in China. Kaplan-Meier survival analysis and Cox regression multivariate analysis models were performed to determine the toxicities and survival outcomes. Results: A total of 463 patients with stage III-IV EOC were enrolled. According to the propensity scores (1:2), 85 patients who received intraperitoneal plus intravenous chemotherapy (group A) were matched to 170 patients who received intravenous chemotherapy (group B). The median follow-up time was 41 months (range 6-155 months). However, there was no statistically significant difference in the median progression-free survival (PFS) (20 vs. 22 months, P = 0.351) or 3-year overall survival (OS) rate (80 vs. 78%, P = 0.749) between the two groups. R0 primary cytoreductive surgery was the only factor related to PFS (P = 0.028) and OS (P = 0.005) by Cox regression analysis. The incidence of grade 3/4 adverse events did not significantly differ between the two groups. Conclusion: The efficacy of intraperitoneal chemotherapy mainly comes from the intraperitoneal drug dose intensity and cumulative dose. High-efficiency and low-toxicity intraperitoneal chemotherapy regimens still need to be found and validated.