Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab.

Background: Camrelizumab, a programmed death 1 (PD-1) inhibiting antibody, has demonstrated efficacy in various malignancies and received approval in multiple countries. Despite its therapeutic benefits, camrelizumab is associated with a unique spectrum of immune-related adverse effects (irAEs), predominantly reactive cutaneous capillary endothelial proliferation (RCCEP). However, visceral manifestations of such endothelial proliferations, particularly hepatic cavernous hemangiomas, have not been extensively documented. Methods: This case series retrospectively reviews six patients who developed hepatic hemangiomas following treatment with camrelizumab in combination with other chemotherapeutic agents. The series highlights the clinical course, imaging findings, management strategies, and outcomes associated with this complication. A detailed analysis was conducted to discern the potential causal relationship between camrelizumab therapy and the development of hepatic hemangiomas. Results: All six patients, after varying cycles of camrelizumab-based therapy, presented with hepatic lesions identified as cavernous hemangiomas on imaging. These findings were atypical for metastatic disease and were further complicated by significant clinical events, including massive intra-abdominal bleeding post-biopsy. Discontinuation of camrelizumab led to a reduction in the size of the hemangiomas in two cases, suggesting a potential link between the drug and the development of these vascular lesions. The incidence of RCCEP remained high, and the use of other agents such as bevacizumab did not mitigate the occurrence of hepatic hemangiomas, indicating a possible unique pathogenic mechanism associated with camrelizumab. Conclusion: Hepatic cavernous hemangioma may represent a rare but clinically significant irAE associated with camrelizumab therapy. This series underscores the importance of vigilant monitoring and a high index of suspicion for atypical hepatic lesions in patients undergoing treatment with PD-1 inhibitors. Further studies are warranted to elucidate the pathophysiology of this complication and to establish guidelines for the management and surveillance of patients receiving camrelizumab.

Role and intervention of PAD4 in NETs in acute respiratory distress syndrome.

BACKGROUND: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Acute respiratory distress syndrome (ARDS) is a common sepsis-associated injury that can increase postoperative mortality but the mechanism is still unclear. MAIN TEXT: The role of neutrophils in the pathophysiology of sepsis was deeply challenged after the discovery of NETosis, a process resulting in neutrophil extracellular traps (NETs) release. NETs can support thrombin generation and the concept of immunothrombosis has emerged as a new innate response to infection. Immunothrombosis leads to thrombosis in microvessels and supports immune cells together with specific thrombus-related molecules. ARDS is a common sepsis-associated organ injury. Immunothrombosis participates in thrombosis in pulmonary capillaries. Intervention regarding immunothrombosis in ARDS is a key scientific problem. PAD4 is the key enzyme regulating the NET skeleton protein histone H3 to citrulline histone to form NETs in immune thrombosis. This review summarizes NETosis and immunohaemostasis, ARDS and therapeutic opportunities targeting PAD4 via PAD4 inhibitors and lncRNAs potentially, providing future therapies. CONCLUSIONS: We identified and summarized the fundamental definition of ARDS and the concept of immune thrombosis and its composition. NETs activation has become particularly relevant in the formation of immune thrombosis. The taskforce highlighted the intervention targets of PAD4, including noncoding RNAs, potentially providing future therapeutic targets to confront the high postoperative mortality of ARDS.

ARID1A deficiency associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes predicts a good prognosis of endometrial carcinoma.

BACKGROUND: ARID1A alterations have been detected in 40% of endometrial carcinomas (ECs) and are associated with loss of its expression. The role of ARID1A in tumorigenesis and development is complex, and the prognostic role in EC remains controversial. Hence, it is of great significance to confirm the role of ARID1A in EC. METHODS: A total of 549 EC patients (cohort A) from TCGA were evaluated to explore the prognostic role of ARID1A. NGS was performed for 13 EC patients (cohort B), and expression of ARID1A, CD3, CD8 and mismatch repair (MMR) proteins in 52 patients (cohort C) from our center was determined by immunohistochemistry (IHC). The Kaplan-Meier method was used to perform survival analyses. RESULTS: ARID1A alterations were detected in 32% of EC patients and correlated with good disease-free survival (DFS, P = 0.004) and overall survival (OS, P = 0.0353). ARID1A alterations were found to co-occur with MMR-related gene mutations and correlated with higher PD-L1 expression. Patients concomitantly harboring ARID1A alterations and MMR-related gene mutations had the best prognosis (DFS: P = 0.0488; OS: P = 0.0024). A cohort from our center showed that ARID1A deficiency was an independent prognostic factor and predicted longer recurrence-free survival (P = 0.0476). ARID1A loss was associated with a tendency toward MSI-H (P = 0.0060). ARID1A alterations and expression loss were associated with a higher abundance of CD3+ (P = 0.0406) and CD8+ (P = 0.0387) T cells. CONCLUSION: ARID1A alterations and expression loss are tightly associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes, which might contribute to the good prognosis of EC.

Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy in stage II-III non-small cell lung cancer: a single-center, single-arm, phase I study in China.

BACKGROUND: Neoadjuvant and adjuvant immune checkpoint inhibitor treatments for non-small cell lung cancer (NSCLC) patients with resectable disease have presented promising results. This is a phase I study to evaluate the safety and efficacy of neoadjuvant toripalimab in combination with chemotherapy for NSCLC. METHODS: Treatment-naive patients with resectable NSCLC (stage II-IIIB) received two to four cycles of toripalimab (240 mg, intravenously, q3w) combined with platinum-paclitaxel chemotherapy. Surgical operation was performed approximately 4 weeks after the last cycle. The primary end point was safety. The efficacy endpoints included radiographic and pathological response rates, expression of programmed death ligand 1 (PD-L1) and molecular targets. RESULTS: A total of 11 patients were enrolled, consisting of 2 patients (18%) with adenocarcinoma and 9 patients (82%) with squamous cell carcinoma. All patients received two to four cycles of toripalimab plus chemotherapy and underwent radical resection. Regarding safety, 5 of 11 patients (45%) had neoadjuvant treatment-related adverse events, and 1 patient (9%) experienced grade 3 or worse treatment-related adverse events. Radiographic partial response was achieved in 10 patients, with an objective response rate of 91%. Among 11 patients, 6 (55%) achieved pathological complete response, including 1 PD-L1-negative patient. CONCLUSION: Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy was tolerable and induced a pathological complete response in 55% of resectable NSCLC patients.

Congenital cholesteatoma clinical and surgical management.

OBJECTIVES: Congenital cholesteatoma (CC) is accompanied by hearing loss and an intact tympanic membrane. However, the hearing loss is usually associated with otitis media, and the diagnosis of CC is frequently delayed in patients with an intact tympanic membrane. This study aimed to describe the clinical characteristics, management and outcomes of patients with CC. METHODS: We reviewed patients with cholesteatoma from January 2011 to May 2020 and selected those meeting the congenital cholesteatoma criteria. The primary outcome measures included presenting symptoms, surgical findings, stage of disease, recurrence rate and hearing outcomes. RESULTS: We reviewed 1646 medical files of cholesteatoma patients and identified 18 patients with congenital cholesteatoma, the mean age at operation was 8.13 ± 1.36 years (range 3-18). The unilateral hearing loss included moderate 13 patients (72.2%), severe 4 patients (22.2%), and slight 1 (5.6%). There were 14 cases of conductive hearing loss (77.8%) and 4 cases of mixed hearing loss (22.2%). The mean course of disease was 1.41 ± 0.05 years (range 0.4-3). The surgical management was oto-endoscope exploratory tympanotomy in 1（5.6%）, canal wall up mastoidectomy in 12 (66.7%) and canal wall down in 5 (27.8%), with 17 (94.4%) ossicular replacements. Seventeen (94.4%) patients presented with Potsic stage III-IV. Recurrence occurred in 5.6% of patients in stage III and 11.1% of patients in stage IV. After surgery, patients achieved normal voice tone hearing. CONCLUSIONS: To diagnose it early, congenital cholesteatoma should be considered as a possible aetiology for hearing loss patients with an intact tympanic membrane. In our study, most patients were diagnosed at III and IV stage. This highlights the need to promote awareness of the disease among primary physicians in the community healthcare system. Surgical management with removal of the cholesteatoma and reconstruction of the tympanum and ossicular chain is an effective treatment.

GenomicKB: a knowledge graph for the human genome.

Genomic Knowledgebase (GenomicKB) is a graph database for researchers to explore and investigate human genome, epigenome, transcriptome, and 4D nucleome with simple and efficient queries. The database uses a knowledge graph to consolidate genomic datasets and annotations from over 30 consortia and portals, including 347 million genomic entities, 1.36 billion relations, and 3.9 billion entity and relation properties. GenomicKB is equipped with a web-based query system (https://gkb.dcmb.med.umich.edu/) which allows users to query the knowledge graph with customized graph patterns and specific constraints on entities and relations. Compared with traditional tabular-structured data stored in separate data portals, GenomicKB emphasizes the relations among genomic entities, intuitively connects isolated data matrices, and supports efficient queries for scientific discoveries. GenomicKB transforms complicated analysis among multiple genomic entities and relations into coding-free queries, and facilitates data-driven genomic discoveries in the future.

First Observation of New Flat Line Fano Profile via an X-Ray Planar Cavity.

A new Fano profile of a flat line is achieved experimentally by manipulating the relative amplitude of the continuum path, when q takes the pure imaginary number of -i in the x-ray regime. The underlying mechanism is that the interference term in the scattering will cancel the discrete term exactly. This new Fano profile renders only an observable continuum along with an invisible response to the discrete state of atomic resonance. The results suggest not only a different strategy to invisibility studies which provides a possible tool to identify weaker structures hidden by the strong white line, but also a new scenario to enrich the manipulations of two-path interference and nonlinear Fano resonance.

Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma.

Our study aimed to explore the efficacy and safety of anlotinib-toripalimab combination therapy as a second-line treatment for advanced relapsed gastric or gastroesophageal junction carcinoma (GC/GEJC). In this single arm, single-center extension clinical trial, patients with advanced relapsed GC/GEJC received toripalimab (240 mg, intravenously over 60 minutes, once every 2 weeks) plus anlotinib (12 mg/day, orally, 2 weeks on and 1 week off, every 3 weeks) as second-line therapy. There were 29 patients who achieved partial response, and the ORR was 32.3% (95% CI, 26.6%-38.5%). Grade 3 treatment-related adverse events (TRAEs) were recorded in 7 participants (11.3%), all of which were manageable. The PFS and OS were 4.0 and 11.1 months, respectively. Patients with programmed death-ligand 1 (PD-L1) positive expression showed numerically longer OS than the negative ones although the difference was not significantly. The tumor mutational burden-high (TMB-H) group showed a significantly better OS (P = .05) than the TMB-Low (TMB-L) group. Next-generation sequencing (NGS) revealed that fibroblast growth factor receptor 2 (FGFR2) mutations positively correlated with target lesion reduction (odds ratio [OR] = 0.14; P = .02). The new regimen increased tumor-infiltration of CD8+ T and CD3+ T cells. Furthermore, a patient-derived organoid (PDO) study indicated that anlotinib could promote an immune-supportive tumor microenvironment. As conclusion, the anlotinib-toripalimab combination showed promising efficacy and favorable safety as a second-line treatment for advanced, relapsed GC/GEJC. The PD-L1 expression, TMB, and FGFR2 mutation are potential biomarkers for predicting the efficacy of this regimen (ClinicalTrials.gov registration number: NCT04713059).

The polymorphism analysis and epitope predicted of Alphapapillomavirus 9 E6 in Sichuan, China.

BACKGROUND: The Alphapapillomavirus 9 (α-9 HPV) is a member of the Alphapapillomavirus genus and Papillomaviridae family. These viruses are almost all carcinogenic HPV, which is closely related to 75% of invasive cervical cancer worldwide, and has a high prevalence in Sichuan. The carcinogenic function is mainly realized by its E6 oncoprotein. METHODS: Cell samples were collected by cervical scraped for HPV detecting and typing. HPV-16, HPV-31, HPV-33, HPV-52, HPV-58 5 α-9 genus HPV subtype positive samples were selected, their E6 gene was sequenced and analyzed. The positive selection sites of HPV E6 genes were estimated by PAML 4.8 server. The secondary and tertiary structure of E6 protein were predicted by PSIPred and Swiss-model. The T-cell antigen epitopes of E6 protein were predicted by IEDB. RESULTS: α-9 HPV has a high prevalence in Sichuan, China. From 2012 to 2017, 18,067 cell cervical samples were collected, and 3135 were detected with α-9 HPV infection. Among which, 250 cases HPV-16 E6, 96 cases HPV-31 E6, 216 cases HPV-33 E6, 288 cases HPV-52 E6 and 405 cases HPV-58 E6 were successfully amplified, 17, 6, 6, 13, and 4 non-synonymous nucleotide mutations were respectively detected in HPV-16, 31, 33, 52, and 58 E6, 7 positive selection sites of α-9 HPV E6 were selected out (D32E of HPV-16 E6, K35N, K93N and R145I of HPV-33 E6, K93R of HPV-52 E6, K93N and R145K of HPV-58 E6). The structure and antigen epitopes of E6 protein with amino acid substitution differ from those of wild-type E6 protein, especially for the mutation located in the E6 positive selection site. CONCLUSIONS: HPV E6 nucleotide non-synonymous mutation in the positive selection site influence the protein structure and decrease the antigen epitopes affinity of the E6 protein overall, making it more difficult for the HPV-infected cells to be detected by the immune system, and enhancing the HPV adaptability to the environment. Mutations influence the validity of HPV clinical diagnostic probes, the polymorphism analysis of α-9 HPV E6 enrich the data of HR-risk HPV in Sichuan China, and the detection probes designed with the polymorphism data in mind can improve the efficiency of clinical detection; Mutations influence epitopes affinity, the association of E6 polymorphism and epitope affinity can improve the design of therapeutic vaccine with good immunity and high generality antigen epitope; The above study all provide a good theoretical basis for the prevention and treatment of HPV-related diseases.

Which BMI for Diabetes Patients is Better? From the View of the Adipose Tissue Macrophage-Derived Exosome.

PURPOSE: Diabetes, as a group of metabolic diseases, can elevate blood glucose, thus leading to the development of life-threatening complications. It is difficult to define the outcome for diabetics with different BMI. This review will illustrate the adipose tissue macrophage-derived exosome in the diabetics with different BMI. PATIENTS AND METHODS: Insulin resistance in peripheral tissues can cause diabetes. The peripheral tissues include liver, muscle, or the adipose depots. Communication between these organs is fatal to the maintenance of glucose homeostasis. This review will illustrate this communication. Obesity is closely linked with diabetes. There are different changes in fat distribution in diabetic patients. Adipose tissue macrophages can secrete various hormones, including adiponectin, leptin, resistin and other classical cytokines, such as TNF-α and IL-6. Studies illustrated that exosomes from the adipose tissue, can modulate inter-organ cross-talk by regulating gene expression in other tissues. RESULTS: Adipose tissue macrophages exosomes links thin and fat individuals in the development of diabetes. CONCLUSION: The molecular pathways initiated by exosomes such as miRNA in the situations of metabolic stress could help us gain a deeper knowledge of the pathophysiology of diabetes.

N6-methyladenosine methylation-related genes YTHDF2, METTL3, and ZC3H13 predict the prognosis of hepatocellular carcinoma patients.

Background: Hepatocellular carcinoma (HCC) is a common primary malignant tumor and cause of cancer-related death in humans. Increasing evidence indicates that an imbalance in N6-methyladenosine (m6A) methylation is strongly linked to the occurrence and development of cancer. We used comprehensive bioinformatics to establish a potential prognostic model of HCC based on m6A methylation-related genes. And case analyses were used to verify the results. Methods: The clinical data and gene expressions were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The prognostic value of m6A methylation-related genes in HCC patients and their relationship with the immune microenvironment were explored by comprehensive bioinformatics analyses. We also collected pathological specimens from 70 patients with HCC from the Department of Pathology, Affiliated Hospital of Qingdao University, and performed immunohistochemical staining on the specimens. We compared tumor specimens from 27 patients positive for METTL3, YTHDF2, and ZC3H13 staining with their adjacent normal tissues and against 27 patient specimens negative for METTL3, YTHDF2, and ZC3H13. The influence of METTL3, YTHDF2, and ZC3H13 on survival was analyzed, and the prognostic model for METTL3, YTHDF2, and ZC3H13 in HCC was verified by clinical data. Results: Most m6A methylation-related genes showed significantly different expressions between cancer and normal tissues. Three candidate m6A methylation-related genes (YTHDF2, METTL3, and ZC3H13) were significantly correlated with the overall survival (OS) of HCC patients. A Kaplan-Meier survival analysis indicated a worse prognosis of high-risk patients than that of low-risk patients. Immunological analysis showed that the high-risk group was more likely to have higher follicular helper T cell counts and lower resting memory CD4 T cell counts. The expression of YTHDF2, METTL3, and ZC3H13 was validated by other databases, including the Oncomine database, the Human Protein Atlas (HPA), and the Kaplan-Meier plotter. Conclusions: Our prognostic model based on m6A methylation-related genes effectively predicted the prognosis of HCC patients.

Anlotinib combined with anti-PD-1 antibody, camrelizumab for advanced NSCLCs after multiple lines treatment: An open-label, dose escalation and expansion study.

OBJECTIVES: Combined therapy should be invested for those patients who are refractory to first-line therapy. Anti-angiogenic agents could enhance tumor immunity response. We designed a phase IB clinical trial and analyzed the effectiveness and safety of anlotinib combined with PD-1inhibitors Camrelizumab for multi-line pretreated and failed advanced NSCLC to explore the synergistic effect of anti-angiogenic agents and immunotherapy. METHODS: All enrolled patients should receive camrelizumab 200 mg every 3 weeks. Eligible patients were randomized successively to three dose cohorts of Anlotinib in a dose escalation clinical setting. Once maximal tolerable dose was established, the primary end point of this study was progression-free survival, overall survival and safety. Risk factor was an exploratory end point. RESULTS: The identified expansion dose for anlotinib was 12 mg. The median PFS of ITT patients was 8.2 months (95% CI, 4.3-12.1 months). And the mOS was 12.7 months (95% CI, 10.2-15.1 months). There was significant difference of mPFS between the 8 mg cohort and the 12 mg cohort (5.6 m vs.11.0 m, p = 0.04). Patients with brain metastasis had a significantly higher risk of death (HR 5.90; 95% CI 2.01-17.30; P = 0.001). Patients whose ECOG was 0 and 1 had a significantly lower risk of death (HR 0.36; 95% CI 0.14-0.91; P = 0.031). CONCLUSIONS: Anlotinib plus camrelizumab had shown promising efficacy and manageable toxicity as a second-line or later-line treatment for NSCLCs, especially in the 12 mg cohorts. Large-scale phase III clinical trials are needed to further explore the rational combination models and biomarkers.

Loss of ARID1A expression promotes lung adenocarcinoma metastasis and predicts a poor prognosis.

BACKGROUND: ARID1A is an essential subunit of SWI/SNF chromatin remodeling complexes. ARID1A gene mutations and loss of ARID1A expression have been observed in a variety of cancers, and to be correlated with invasion, immune escape and synthetic lethality. As yet, however, the biological effect of ARID1A expression and its role in the prognosis of lung adenocarcinoma (LUAD) patients have remained unclear. In this study we aimed to further elucidate the role of ARID1A expression in LUAD in vitro and in vivo and to assess its effect on the clinical prognosis of LUAD patients. METHODS: ARID1A expression was detected by IHC in tissue samples from LUAD patients. After regular culturing of LUAD cell lines and constructing stable ARID1A knockdown lines, wound healing and Transwell assays were used to assess the role of ARID1A in cell migration and invasion. The effect of ARID1A knockdown on metastasis was verified in vivo. Western blotting was used to examine the expression of target proteins. Univariate and multivariate analyses were performed to assess survival and to provide variables for nomogram construction. In addition, we used the "rms" package to construct a prognostic nomogram based on a Cox regression model. RESULTS: We found that ARID1A expression serves as an effective prognostic marker for LUAD patients. Loss of ARID1A expression correlated with a poor prognosis, as verified with a nomogram based on a Cox regression model. In addition, we found that ARID1A knockdown promoted LUAD cell proliferation, migration and invasion in vitro and enhanced LUAD metastasis in vivo by activating the Akt signaling pathway. CONCLUSIONS: Our data indicate that loss of ARID1A expression promotes LUAD metastasis and predicts a poor prognosis in LUAD patients.

Genetic variability of human papillomavirus type 39 based on E6, E7 and L1 genes in Southwest China.

BACKGROUND: Human papillomavirus type 39 associated with genital intraepithelial neoplasia and invasive cancers, has a high prevalence in Southwest China. HPV E6, E7 are two main papillomavirus oncoproteins, closely relate to the function of HPV immortalization, cell transformation, and carcinogenesis. L1 is the major capsid protein, can reflect the replication status of the virus in cells and the progression of cervical lesions. The purpose of this study is to reveal the prevalence of HPV 39 and the genetic polymorphisms of HPV39 based on E6, E7 and L1 gene in southwest China. METHODS: Cell samples were collected by cervical scraped for HPV detecting and typing, and HPV39 positive samples were selected out. Important E6, E7 and L1 genes of HPV39 were sequenced and analyzed for the study of HPV39 genetic polymorphisms. Phylogenetic trees were constructed by Maximum-likelihood and Kimura 2-parameters methods in Molecular Evolutionary Genetics Analysis version 6.0. The selection pressures of E6, E7 and L1 genes were estimated by Datamonkey web server. The secondary and three-dimensional structure of HPV39 E6, E7 proteins were created by sopma server and SWISS-MODEL software. RESULTS: 344 HPV39 positive samples were selected from 5718 HPV positive cell samples. Among HPV39 E6-E7 sequences, 20 single nucleotide mutations were detected, including 10 non-synonymous and 10 synonymous mutations; 26 single nucleotide mutations were detected in HPV39 L1 sequences, including 7 non-synonymous and 19 synonymous mutations respectively. 11 novel variants of HPV39 E6-E7 (5 in E6 and 6 in E7) and 14 novel variants of HPV39 L1 were identified in this study. A-branch was the most frequent HPV39 lineage in southwest China during our investigation. Selective pressure analysis showed that codon sites 26, 87, 151 in E6 and 75, 180, 222, 272, 284, 346, 356 in L1 were positively selected sites, as well as codon sites 45, 138, 309, 381 were negative selection sites in L1 gene, E7 has neither positive selection sites nor negative selection sites. A certain degree of secondary and three-dimensional structure dislocation was existed due to the non-synonymous mutations. CONCLUSIONS: Amino acid substitution affected the secondary and three-dimensional structure of HPV39, and resulting in the differences of carcinogenic potential and biological functions as well as the immune response due to the antigen epitopes difference, the antigen epitopes with stronger adaptability in Southwest will be screened out based on the above research results for the later vaccine development. And gene polymorphism of HPV39 in Southwest China may improve the effectiveness of clinical test and vaccine design, specifically for women in Southwest China.

Searching for Solar Axions Using Data from the Sudbury Neutrino Observatory.

We explore a novel detection possibility for solar axions, which relies only on their couplings to nucleons, via the axion-induced dissociation of deuterons into their constituent neutrons and protons. An opportune target for this process is the now-concluded Sudbury Neutrino Observatory (SNO) experiment, which relied upon large quantities of heavy water to resolve the solar neutrino problem. From the full SNO dataset we exclude in a model-independent fashion isovector axion-nucleon couplings |g_{aN}^{3}|≡1/2|g_{an}-g_{ap}|>2×10^{-5} GeV^{-1} at 95% C.L. for sub-MeV axion masses, covering previously unexplored regions of the axion parameter space. In the absence of a precise cancellation between g_{an} and g_{ap} this result also exceeds comparable constraints from other laboratory experiments, and excludes regions of the parameter space for which astrophysical constraints from SN1987A and neutron star cooling are inapplicable due to axion trapping.

Use tumor suppressor genes as biomarkers for diagnosis of non-small cell lung cancer.

Lung cancer is the leading cause of death worldwide. Especially, non-small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efficient biomarkers for detection, diagnosis and prognosis. To find high efficient biomarkers for clinical diagnosis of NSCLC patients, we used gene differential expression and gene ontology (GO) to define a set of 26 tumor suppressor (TS) genes. The 26 TS genes were down-expressed in tumor samples in cohorts GSE18842, GSE40419, and GSE21933 and at stages 2 and 3 in GSE19804, and 15 TS genes were significantly down-expressed in tumor samples of stage 1. We used S-scores and N-scores defined in correlation networks to evaluate positive and negative influences of these 26 TS genes on expression of other functional genes in the four independent cohorts and found that SASH1, STARD13, CBFA2T3 and RECK were strong TS genes that have strong accordant/discordant effects and network effects globally impacting the other genes in expression and hence can be used as specific biomarkers for diagnosis of NSCLC cancer. Weak TS genes EXT1, PTCH1, KLK10 and APC that are associated with a few genes in function or work in a special pathway were not detected to be differentially expressed and had very small S-scores and N-scores in all collected datasets and can be used as sensitive biomarkers for diagnosis of early cancer. Our findings are well consistent with functions of these TS genes. GSEA analysis found that these 26 TS genes as a gene set had high enrichment scores at stages 1, 2, 3 and all stages.

The Study of the Low-Lying Valence-Shell Excitations of Hydrogen Sulfide by Fast Electron Impact.

The valence-shell excitations of hydrogen sulfide have been studied by fast electron impact at a collision energy of 1.5 keV and an energy resolution of about 70 meV. By analyzing the variations of intensity and shape of the feature in the range of 5.0-7.5 eV at different scattering angles, the excitation energy of 5.85 ± 0.01 eV and the line width of 0.80 ± 0.01 eV of the 3b21A2 state have been determined. The generalized oscillator strengths of the valence-shell excitations in the energy range of 5.0-9.2 eV of hydrogen sulfide have been determined from the measured spectra. The corresponding optical oscillator strengths have been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The integral cross sections have also been systematically determined from the threshold to 5000 eV by means of the BE-scaling method. The presently obtained oscillator strengths and integral cross sections have significant applications in the studies of planetary atmospheres and interstellar gases.

Risk factors and the potential of nomogram for predicting hospital-acquired pressure injuries.

This 1:5 case-control study aimed to identify the risk factors of hospital-acquired pressure injuries (HAPIs) and to develop a mathematical model of nomogram for the risk prediction of HAPIs. Data for 370 patients with HAPIs and 1971 patients without HAPIs were extracted from the adverse events and the electronic medical systems. They were randomly divided into two sets: training (n = 1951) and validation (n = 390). Significant risk factors were identified by univariate and multivariate analyses in the training set, followed by a nomogram constructed. Age, independent movement, sensory perception and response, moisture, perfusion, use of medical devices, compulsive position, hypoalbuminaemia, an existing pressure injury or scarring from a previous pressure injury, and surgery sufferings were considered significant risk factors and were included to construct a nomogram. In both of the training and validation sets, the areas of 0.90 under the receiver operating characteristic curves showed excellent discrimination of the nomogram; calibration plots demonstrated a good consistency between the observed probability and the nomogram's prediction; decision curve analyses exhibited preferable net benefit along with the threshold probability in the nomogram. The excellent performance of the nomogram makes it a convenient and reliable tool for the risk prediction of HAPIs.

The Effect of Waste Engine Oil and Waste Polyethylene on UV Aging Resistance of Asphalt.

Waste engine oil (WEO) and waste polyethylene (WPE) are two common wastes, which are easy to pollute the environment. As the primary material in road construction, natural asphalt is a non-renewable energy source and asphalt is vulnerable to ultraviolet (UV) radiation during the service life. It results in degradation of asphalt pavement performance. In this paper, 22 wt % to 82 wt % of WEO and WPE were used to modify asphalts and the UV aging simulation experiment was carried out. The physical parameters of asphalts before the UV aging experiment show that the asphalt containing 42 wt % WPE and 62 wt % WEO mixture (42 wt % WPE + 62 wt % WEO) has similar physical properties with that of the matrix asphalt. Besides, gel permeation chromatography (GPC) verifies that the molecular weight distribution of the asphalt containing 42 wt % WPE + 62 wt % WEO is close to that of the matrix asphalt. The storage stability test shows that 42 wt % WPE + 62 wt % WEO has good compatibility with the matrix asphalt. The functional groups and micro-morphology of asphalts before and after the UV aging experiment were investigated by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). FTIR results display that 42 wt % WPE + 62 wt % WEO can effectively reduce the formation of carbonyl and sulfoxide functional groups. AFM shows that 42 wt % WPE + 62 wt % WEO can also retard the formation of a "bee-like" structure in asphalt after the UV aging experiment. Based on the above results, it can be concluded that WEO and WPE mixture can replace part of asphalt and improve the UV aging resistance of asphalt.

Prevention and Control of Pathogens Based on Big-Data Mining and Visualization Analysis.

Morbidity and mortality caused by infectious diseases rank first among all human illnesses. Many pathogenic mechanisms remain unclear, while misuse of antibiotics has led to the emergence of drug-resistant strains. Infectious diseases spread rapidly and pathogens mutate quickly, posing new threats to human health. However, with the increasing use of high-throughput screening of pathogen genomes, research based on big data mining and visualization analysis has gradually become a hot topic for studies of infectious disease prevention and control. In this paper, the framework was performed on four infectious pathogens (Fusobacterium, Streptococcus, Neisseria, and Streptococcus salivarius) through five functions: 1) genome annotation, 2) phylogeny analysis based on core genome, 3) analysis of structure differences between genomes, 4) prediction of virulence genes/factors with their pathogenic mechanisms, and 5) prediction of resistance genes/factors with their signaling pathways. The experiments were carried out from three angles: phylogeny (macro perspective), structure differences of genomes (micro perspective), and virulence and drug-resistance characteristics (prediction perspective). Therefore, the framework can not only provide evidence to support the rapid identification of new or unknown pathogens and thus plays a role in the prevention and control of infectious diseases, but also help to recommend the most appropriate strains for clinical and scientific research. This paper presented a new genome information visualization analysis process framework based on big data mining technology with the accommodation of the depth and breadth of pathogens in molecular level research.