Establishment of a risk prediction model for olfactory disorders in patients with transnasal pituitary tumors by machine learning.

To construct a prediction model of olfactory dysfunction after transnasal sellar pituitary tumor resection based on machine learning algorithms. A cross-sectional study was conducted. From January to December 2022, 158 patients underwent transnasal sellar pituitary tumor resection in three tertiary hospitals in Sichuan Province were selected as the research objects. The olfactory status was evaluated one week after surgery. They were randomly divided into a training set and a test set according to the ratio of 8:2. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. Based on different machine learning algorithms, BP neural network, logistic regression, decision tree, support vector machine, random forest, LightGBM, XGBoost, and AdaBoost were established to construct olfactory dysfunction risk prediction models. The accuracy, precision, recall, F1 score, and area under the ROC curve (AUC) were used to evaluate the model's prediction performance, the optimal prediction model algorithm was selected, and the model was verified in the test set of patients. Of the 158 patients, 116 (73.42%) had postoperative olfactory dysfunction. After missing value processing and feature screening, an essential order of influencing factors of olfactory dysfunction was obtained. Among them, the duration of operation, gender, type of pituitary tumor, pituitary tumor apoplexy, nasal adhesion, age, cerebrospinal fluid leakage, blood scar formation, and smoking history became the risk factors of olfactory dysfunction, which were the key indicators of the construction of the model. Among them, the random forest model had the highest AUC of 0.846, and the accuracy, precision, recall, and F1 score were 0.750, 0.870, 0.947, and 0.833, respectively. Compared with the BP neural network, logistic regression, decision tree, support vector machine, LightGBM, XGBoost, and AdaBoost, the random forest model has more advantages in predicting olfactory dysfunction in patients after transnasal sellar pituitary tumor resection, which is helpful for early identification and intervention of high-risk clinical population, and has good clinical application prospects.

The effect of occupational coping self-efficacy on presenteeism among ICU nurses in Chinese public hospitals: a cross-sectional study.

Background: Nurses are the largest occupational group in the health field, with inestimable value in realizing universal health coverage, and nurses' physical and mental health has become an ordinary global reality. Compared with explicit absence, nurses' presenteeism has a more lasting impact and significant harm and loss. It has become an essential factor affecting nurses' physical and mental health, declining quality of healthcare services, and elevated healthcare-related risks. There is a lack of research exploring whether occupational coping self-efficacy influences nurses' presenteeism behavior, especially in less-developed regions of China. Objective: This study aimed to investigate the current status of ICU nurses' occupational coping self-efficacy and presenteeism in public hospitals in western China and to explore the impact of ICU nurses' occupational coping self-efficacy on presenteeism. Methods: A cross-sectional research design selected 722 ICU nurses in western China from January to February 2023 as survey respondents. A general information questionnaire, Occupational Coping Self-Efficacy Scale (OCSE-N), and Stanford Presenteeism Scale (SPS-6) were used. SPSS 21.0 software was used for statistical analysis. Pearson correlation analysis and multivariate hierarchical regression were used to explore the influence of ICU nurses' occupational coping self-efficacy on presenteeism. Results: A total of 722 ICU nurses completed the questionnaire. The OCSE-N score of ICU nurses was (22.24 ± 6.15), and the SPS-6 score was (16.83 ± 4.24). The high presenteeism was 67.23%. Correlation analysis showed that in ICU nurses, OCSE-N total score was negatively correlated with SPS-6 total score (r = -0.421, p < 0.05), indicating that the higher the level of occupational coping self-efficacy, the lower the presenteeism. Multiple hierarchical regression analysis showed that occupational coping self-efficacy strongly predicted presenteeism, accounting for approximately 18.35% of the total variance. Conclusion: There is a correlation between ICU nurses' occupational coping self-efficacy and presenteeism, and nurses' occupational coping self-efficacy affects presenteeism differently. Managers should pay attention to nurses' occupational coping self-efficacy to promote nurses' presenteeism reduction.

Evaluation of routine proximal bone analysis for microbiology and histopathology in diabetes-related foot infections and osteomyelitis.

PURPOSE: The value of proximal bone analysis for surgical clearance of infection remains debated. Real-world practice traditionally utilized proximal bone microbiology rather than histopathology to diagnose residual diabetes-related osteomyelitis of the foot (DFO) post-amputation. We assessed the concordance between proximal bone microbiology and histopathology in determining residual infection and their predictability for revision operation in DFO and diabetes-related foot infection (DFI). METHODOLOGY: A single-centre retrospective study was conducted between June and December 2020 at a tertiary institution. We recruited patients with diabetes mellitus who had minor amputations for DFO and DFI and analyzed their proximal bone microbiology, histopathology and outcomes at 6 months. RESULTS: Eighty-four patients were recruited; 64 (76.2%) were male. The mean age was 69.3 years. The mean HbA1c was 8.6%. Seventy-seven operations were performed for DFO and 17 for DFI. Negative microbiology showed complete concordance with histopathology; and none had revision operation (P = 0.99). Positive microbiology had 9.8% concordance with histopathology (P = 0.99). Positive histopathology was associated with a higher rate of revision operation (80% vs. 12.5%; P = 0.01). High preoperative C-reactive protein was associated with residual DFO (P = 0.02) and revision operation (P = 0.01). CONCLUSION: Positive histopathology was more reliable for determining significant residual DFO and predicting revision operation. Positive microbiology was valuable for guiding antibiotic selection. We suggest routine proximal bone analysis for both histopathology and microbiology to optimize the treatment of DFO and DFI.

Smart Target-Initiated Catalytic DNA Junction Circuit Amplification Strategy for the Ultrasensitive Electrochemiluminescence Detection of MicroRNA.

One of the highly attractive research directions in the electrochemiluminescence (ECL) field is how to regulate and improve ECL efficiency. Quantum dots (QDs) are highly promising ECL materials due to their adjustable luminescence size and strong luminous efficiency. MoS2 NSs@QDs, an ECL emitter, is synthesized via hydrothermal methods, and its ECL mechanism is investigated using cyclic voltammetry and ECL-potential curves. Then, a stable and vertical attachment of a triplex DNA (tsDNA) probe to the MoS2 nanosheets (NSs) is applied to the electrode. Next, an innovative ECL sensor is courageously empoldered for precise and ultrasensitive detection of target miRNA-199a through the agency of ECL-resonance energy transfer (RET) strategy and a dextrous target-initiated catalytic three-arm DNA junction assembly (CTDJA) based on a toehold strand displacement reaction (TSDR) signal amplification approach. Impressively, the ingenious system not only precisely regulates the distance between energy donor-acceptor pairs leave energy less loss and more ECL-RET efficiency, but also simplifies the operational procedure and verifies the feasibility of this self-assembly process without human intervention. This study can expand MoS2 NSs@QDs utilization in ECL biosensing applications, and the proposed nucleic acid amplification strategy can become a miracle cure for ultrasensitive detecting diverse biomarkers, which helps researchers to better study the tumor mechanism, thereby unambiguously increasing cancer cure rates and reducing the risk of recurrence.

Gene cloning and molecular characterization of a thermostable chitosanase from Bacillus cereus TY24.

BACKGROUND: An important conceptual advance in health and the environment has been recognized that enzymes play a key role in the green processing industries. Of particular interest, chitosanase is beneficial for recycling the chitosan resource and producing chitosan oligosaccharides. Also, chitosan gene expression and molecular characterization will promote understanding of the biological function of bacterial chitosanase as well as explore chitosanase for utilizing chitosan resources. RESULTS: A chitosanase-producing bacterium TY24 was isolated and identified as Bacillus cereus. Moreover, the chitosanase gene was cloned and expressed in Escherichia coli. Sequence analysis reveals that the recombinant chitosanase (CHOE) belongs to the glycoside hydrolases 8 family. The purified CHOE has a molecular weight of about 48 kDa and the specific activity of 1150 U/mg. The optimal pH and temperature of CHOE were 5.5 and 65 °C, respectively. The enzyme was observed stable at the pH range of 4.5-7.5 and the temperature range of 30-65 °C. Especially, the half-life of CHOE at 65 °C was 161 min. Additionally, the activity of CHOE was remarkably enhanced in the presence of Mn2+, Cu2+, Mg2+ and K+, beside Ca2+ at 5 mM. Especially, the activity of CHOE was enhanced to more than 120% in the presence of 1% of various surfactants. CHOE exhibited the highest substrate specificity toward colloid chitosan. CONCLUSION: A bacterial chitosanase was cloned from B. cereus and successfully expressed in E. coli (BL21) DE3. The recombinant enzyme displayed good stability under acid pH and high-temperature conditions.

Production of surfactant-stable keratinase from Bacillus cereus YQ15 and its application as detergent additive.

BACKGROUND: With the growing concern for the environment, there are trends that bio-utilization of keratinous waste by keratinases could ease the heavy burden of keratinous waste from the poultry processing and leather industry. Especially surfactant-stable keratinases are beneficial for the detergent industry. Therefore, the production of keratinase by Bacillus cereus YQ15 was improved; the characterization and use of keratinase in detergent were also studied. RESULTS: A novel alkaline keratinase-producing bacterium YQ15 was isolated from feather keratin-rich soil and was identified as Bacillus cereus. Based on the improvement of medium components and culture conditions, the maximum keratinase activity (925 U/mL) was obtained after 36 h of cultivation under conditions of 35 °C and 160 rpm. Moreover, it was observed that the optimal reacting temperature and pH of the keratinase are 60 °C and 10.0, respectively; the activity was severely inhibited by PMSF and EDTA. On the contrary, the keratinase showed remarkable stability in the existence of the various surfactants, including SDS, Tween 20, Tween 60, Tween 80, and Triton X-100. Especially, 5% of Tween 20 and Tween 60 increased the activity by 100% and 60%, respectively. Furtherly, the keratinase revealed high efficiency in removing blood stains. CONCLUSION: The excellent compatibility with commercial detergents and the high washing efficiency of removing blood stains suggested its suitability for potential application as a bio-detergent additive.

Targeting IRAK3 for Degradation to Enhance IL-12 Pro-inflammatory Cytokine Production.

Interleukin-1 receptor-associated kinase 3 (IRAK3) is a pseudokinase mediator in the human inflammatory pathway, and ablation of its function is associated with enhanced antitumor immunity. Traditionally, pseudokinases have eluded "druggability" and have not been considered tractable targets in the pharmaceutical industry. Herein we disclose a CRISPR/Cas9-mediated knockout of IRAK3 in monocyte-derived dendritic cells that results in an increase in IL-12 production upon lipopolysaccharide (LPS) stimulation. Furthermore, we disclose and characterize Degradomer D-1, which displays selective proteasomal degradation of IRAK3 and reproduces the 1L-12p40 increases observed in the CRISPR/Cas9 knockout.

Effects of Substrate Surface Characteristics on the Adhesion Properties of Geopolymer Coatings.

Geopolymer is a kind of material with a better ability of high-temperature and corrosion resistance. Poor adhesion could easily lead to problems such as coating cracks, peeling at an early stage, and inability to work with the substrate. The adhesion depends on many factors such as chemical composition of the raw materials, the formulation of the geopolymer, the type of substrate, surface roughness of the substrate, etc. The higher the Si/Al ratio, the greater the shear strength of the coating. This is because geopolymers synthesized with different Si/Al ratios have different phases in the geopolymer binder. Each study uses different multi-parameter combinations selected by itself, which is not uniform and has no universal applicability. As the parameter Ra is determined by the profile centerlines of the substrate surface, it is difficult to get an appropriate value of Ra to represent the roughness of the substrate surface. The parameter-relative area, determined by area scale fractal analysis, can effectively characterize the surface roughness, predict the texture component of bond strength, and establish a connection between which and the bonding performance of the geopolymer coating at a high level of confidence. The bonding strength reduces with the decrease in the value of the relative area. The magnitude of scale employed should be seriously determined when characterizing the surface roughness.

Pooled analysis of LAMP assay for the diagnosis of norovirus infection.

BACKGROUND: Rapid laboratory detection is essential to diagnose norovirus infection. LAMP has many advantages compared with RT-PCR for detecting norovirus, including high sensitivity, high specificity, rapidity, low cost, and intuitive results, which can be easily read with the naked eye with the help of color-based reporters. In this study, we intend to analyze the accuracy of LAMP methods for the diagnosis of norovirus infection. METHODS: Two researchers independently retrieved relevant literature up to January 2021 (PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wan Fang, and VIP). The researchers screened all articles and extracted their research data for meta-analysis. QUADAS-2 tool was used to evaluate the quality of the included studies by Review Manager 5.3. Forest plots were performed by Meta-DiSc 1.4 to evaluate the accuracy of the test. Deeks' funnel plot symmetry tests were conducted by Stata 15.0 to check the potential publication bias. RESULTS: Eleven sets of data extracted from the eight included studies were included for meta-analysis. For the detection of norovirus, the pooled sensitivity, specificity, positive LR, negative LR, diagnostic OR, and their 95% CI were 0.96 (0.95-0.97), 0.99 (0.99-1.00), 91.14 (31.88-260.56), 0.06 (0.04-0.09), and 1473.68 (562.96-3857.70), respectively. Besides, AUC in the SROC curve was 0.9920. CONCLUSION: LAMP had high sensitivity and specificity in terms of the diagnosis of norovirus infection. However, further extension of this approach should be researched to ensure the accuracy and practicability of this hopeful test in the future.

Review on the Adhesion of Geopolymer Coatings.

Geopolymers are considered to be green materials with excellent fire resistance performance and potential substitutes for ordinary Portland cement (OPC). This review article focuses on the adhesion of geopolymer coatings subjected to elevated temperature. Their high adhesion strength is the basis for geopolymers being used as coating materials to work with the substrate. The adhesion strength is related to many factors, such as chemical composition of the raw materials, the formulation of the geopolymer, substrate type, surface roughness of the substrate, etc. The Si/Al ratio has different effects on compressive strength and bonding strength. The water content affects the polymerization process-the adhesion strength decreases with increasing water content. Careful tailoring of the mix ratio design is essential to make the geopolymer coating have excellent adhesive performance. These mix design factors include Si/Al ratio, Al/Na ratio, water content, precursor type, alkali cation type, curing conditions, etc.

Optimal designs for discrete-time survival models with random effects.

This paper considers the optimal design for the frailty model with discrete-time survival endpoints in longitudinal studies. We introduce the random effects into the discrete hazard models to account for the heterogeneity between experimental subjects, which causes the observations of the same subject at the sequential time points being correlated. We propose a general design method to collect the survival endpoints as inexpensively and efficiently as possible. A cost-based generalized D ([Formula: see text])-optimal design criterion is proposed to derive the optimal designs for estimating the fixed effects with cost constraint. Different computation strategies based on grid search or particle swarm optimization (PSO) algorithm are provided to obtain generalized D ([Formula: see text])-optimal designs. The equivalence theorem for the cost-based D ([Formula: see text])-optimal design criterion is given to verify the optimality of the designs. Our numerical results indicate that the presence of the random effects has a great influence on the optimal designs. Some useful suggestions are also put forward for future designing longitudinal studies.

Clinical and imaging features of middle ear hairy polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To collect the clinical cases of middle ear hairy polyp, and to summarize the imaging features. Methods: We retrospectively analyzed the clinical data of four cases middle ear hairy polyp confirmed by surgical and pathologic between January 2007 and January 2020 at the Affiliated Eye & ENT Hospital of Fudan University. There were three females, one male, with two left ears and two right ears, aged from 1 to 59 years. The CT and MRI imaging of the patients, and the corresponding clinical manifestations were analyzed. Results: Hairy polyps originated from tympanum in one case, originated from Eustachian tube in two cases, exhibiting recurrent otorrhea without evident inducement. The other case, hairy polyps originated from the Eustachian tube pharyngeal orifice and protruded into the nasopharyngeal cavity, with pharynx discomfort and aural fullness, endoscope showed offwhite polypoid mass with a little hair. All the four cases presented polypoid soft tissue masses on CT and MRI imaging, containing soft tissue wall and a large amount of adipose tissue, with soft tissue in the center of the mass which liked the core, and enhanced. MRI showed stratified arrangement of fat and soft tissue in the wall of the mass. Four cases all had surgical treatment, postoperative pathology examination presented that hair follicles, mature sebaceous glands and other skin appendages were found under squamous epithelium. A large amount of adipose tissue, part of muscle tissue, cartilage tissue, and some fibro-collagenous tissue were proliferated in the mass, accompanied by collagen degeneration. Conclusion: The middle ear hairy polyps has imaging characteristics, the polypoid soft tissue mass usually looks smooth and contains a large amount of adipose tissue, with a soft tissue in the center, and can be suggestively diagnosed by CT and MRI.

Recombinant expression and molecular engineering of the keratinase from Brevibacillus parabrevis for dehairing performance.

Keratinase is capable of distinctive degradation of keratin, which provides an eco-friendly approach for keratin waste management towards sustainable development. In this study, the recombinant keratinase (KERBP) from Brevibacillus parabrevis was successfully expressed in Escherichia coli. The purified KERBP had the specific activity of 6005.3 U/mg. It showed remarkable tolerance to various surfactants and also no collagenolytic activity. However, the moderate thermal stability limited its further application. Thus, protein engineering was further adopted to improve its stability. The variants of T218S, S236C and N181D were constructed by site-directed mutagenesis and combinatorial mutagenesis. Compared with the wild type, the t1/2 at 60 °C for the variants T218S, S236C and N181D were 3.05-, 1.18- and 1-fold increase, respectively. Moreover, the double variants N181D-T218S and N181D-S236C significantly improved thermostability with 5.1 and 2.9 °C increase of T50, and prolonging t1/2 at 60 °C with 4.09 and 1.54-fold, respectively. And the catalytic efficiency of the T218S and N181D-T218S variants was also significantly improved. Furthermore, the keratinase displayed favorable ability to dehair wool from skin within 7 h, which showed potential in leather dehairing. Our work contributes to a further insight into the thermostability of keratinase and offers a promising alternative for industrial leather application.

The Clinical and Molecular Characteristics of FLT3 Mutations in Chinese De Novo Adolescent and Adult Acute Lymphoblastic Leukemia Patients.

BACKGROUND: Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are frequent in acute myeloid leukemia (AML) and have important prognostic and therapeutic implications. FLT3 aberrations have been detected in a smaller fraction of acute lymphoblastic leukemia (ALL), and their prognostic value is not well established. We therefore assessed the FLT3 mutation in Chinese adolescent and adult ALL patients. PATIENTS AND METHODS: We have examined a cohort of 117 Chinese de novo adolescent and adult ALL patients enrolled between June 2016 and June 2017 from the First Affiliated Hospital of Soochow University. Prognostic factors for the ALL patient population were estimated by the Cox regression method. FLT3 mutation was detected by PCR, and its clinical effect was assessed by Kaplan-Meier curves. Differences in FLT3 mutation rate between subgroups were tested by chi-square test. RESULTS: FLT3 mutations accounted for 6.8% (8/117) in our cohort, including 3 internal tandem duplications (2.6%) and 5 tyrosine kinase domains (4.3%, 3 D835Y mutations, 1 M664I mutation, and 1 I867S mutation), which had no clinical significance on either overall survival (OS) or event-free survival. Alterations in FLT3 occurred more often in early thymic precursor (ETP)-ALL compared to non-ETP T-cell acute lymphoblastic leukemia (P = .028). However, the age at onset (P = .004), initial platelet counts (P = .018), and transplantation status (P = .007) were independent prognostic factors of OS for ALL in multivariate analysis. CONCLUSION: The FLT3 mutation was not common in Chinese ALL patients. Age at onset, platelet counts, and transplantation status rather than the presence of the FLT3 mutation were independent prognostic variables for ALL on OS in our cohort. Despite our small sample size, ETP-ALL may indicate a comparable higher FLT3-mutant rate. Because ETP-ALL has been identified as high-risk subgroup, these data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic hematopoietic stem-cell transplantation for FLT3-mutant ETP-ALL.

Establishment of an efficient reverse genetic system of Mumps virus S79 from cloned DNA.

BACKGROUND: Mumps is a common type of respiratory infectious disease caused by mumps virus (MuV), and can be effectively prevented by vaccination. In this study, a reverse genetic system of MuV that can facilitate the rational design of safer, more efficient mumps vaccine candidates is established. METHODS: MuV-S79 cDNA clone was assembled into a full-length plasmid by means of the GeneArt™ High-Order Genetic Assembly System, and was rescued via reverse genetic technology. RT-PCR, sequencing, and immunofluorescence assays were used for rMuV-S79 authentication. Viral replication kinetics and in vivo experimental models were used to evaluate the replication, safety, and immunogenicity of rMuV-S79. RESULTS: A full-length cDNA clone of MuV-S79 in the assembly process was generated by a novel plasmid assemble strategy, and a robust reverse genetic system of MuV-S79 was successfully established. The established rMuV-S79 strain could reach a high virus titer in vitro. The average viral titer of rMuV-S79 in the lung tissues was 2.68 ± 0.14 log10PFU/g lung tissue, and rMuV-S79 group did not induce inflammation in the lung tissues in cotton rats. Neutralizing antibody titers induced by rMuV-S79 were high, long-lasting and could provide complete protection against MuV wild strain challenge. CONCLUSION: We have established a robust reverse genetic system of MuV-S79 which can facilitate the optimization of mumps vaccines. rMuV-S79 rescued could reach a high virus titer and the safety was proven in vivo. It could also provide complete protection against MuV wild strain challenge.

Iizukines C-E from a saline soil fungus Aspergillus iizukae.

Three new alkaloids, iizukines C-E (1-3), including two aspochalasins (1 and 2), and one brasiliamide derivative (3), along with two known aspochalasins, rosellichalasin (4) and cytochalasin Z17 (5), were isolated from the culture of Aspergillus iizukae. Compound 1 was the first aspochalasin uniquely featuring a 1,2,4-triazole functionality, and 3 showed a pair of NMR signals in CDCl3 with a ratio of about 2:1 due to the existence of conformational isomers. Their structures were determined by extensive spectroscopic analyses and single-crystal X-ray diffractions. In particular, the 1,2,4-triazole moiety in 1 was assigned on the basis of extremely valuable 1H-15N HMBC spectrum. Compound 1 exhibited cytotoxic effect towards HL-60 and A549 cell lines with IC50 values of 3.8 and 7.2 µM, respectively.

Attenuated MuV-S79 as vector stably expressing foreign gene.

BACKGROUND: To describe mumps virus (MuV) used as a vector to express enhanced green fluorescent protein (EGFP) or red fluorescent protein (RFP) genes. METHODS: Molecular cloning technique was applied to establish the cDNA clones of recombinant mumps viruses (rMuVs). rMuVs were recovered based on our reverse genetic system of MuV-S79. The properties of rMuVs were determined by growth curve, plaque assay, fluorescent microscopy and determination of fluorescent intensity. RESULTS: Three recombinant viruses replicated well in Vero cells and similarly as parental rMuV-S79, expressed heterologous genes in high levels, and were genetically stable in at least 15 passages. CONCLUSION: rMuV-S79 is a promising platform to accommodate foreign genes like marker genes, other antigens and immunomodulators for addressing various diseases.

A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains.

Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.