Discovery and genetic characterization of novel paramyxoviruses from small mammals in Hubei Province, Central China.

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.

Comparative study of two indoor microbial volatile pollutants, 2-Methyl-1-butanol and 3-Methyl-1-butanol, on growth and antioxidant system of rice (Oryza sativa) seedlings.

2-Methyl-1-butanol (2MB) and 3-Methyl-1-butanol (3MB) are microbial volatile organic compounds (VOCs) and found in indoor air. Here, we applied rice as a bioindicator to investigate the effects of these indoor microbial volatile pollutants. A remarkable decrease in germination percentage, shoot and root elongation, as well as lateral root numbers were observed in 3MB. Furthermore, ROS production increased by 2MB and 3MB, suggesting that pentanol isomers could induce cytotoxicity in rice seedlings. The enhancement of peroxidase (POD) and catalase (CAT) activity provided evidence that pentanol isomers activated the enzymatic antioxidant scavenging systems, with a more significant effect observed in 3MB. Furthermore, 3MB induced higher activity levels of glutathione (GSH), oxidized glutathione (GSSG), and the GSH/GSSG ratio in rice compared to the levels induced by 2MB. Additionally, qRT-PCR analysis showed more up-regulation in the expression of glutaredoxins (GRXs), peroxiredoxins (PRXs), thioredoxins (TRXs), and glutathione S-transferases (GSTUs) genes in 3MB. Taking the impacts of pentanol isomers together, the present study suggests that 3MB exhibits more cytotoxic than 2MB, as such has critical effects on germination and the early seedling stage of rice. Our results provide molecular insights into how isomeric indoor microbial volatile pollutants affect plant growth through airborne signals.

Oxytocin and vaginal dinoprostone in labor induction: A systematic review and meta-analysis.

BACKGROUND: The comparison between prostaglandin E2 (PGE2) and oxytocin and for induction of labor (IOL) remains controversial. OBJECTIVE: The present study aimed to determine the safety and efficacy of these two agents in IOL. SEARCH STRATEGY: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. from the establishment of the database to April 23, 2023. SELECTION CRITERIA: A search was conducted with keywords "labor, induction, prostaglandin E2/PGE2/dinoprostone, and oxytocin". Only randomized clinical trials comparing oxytocin and vaginal dinoprostone in women who were at least late preterm (gestational age [GA] ≥34 weeks), singleton pregnant, and had intact membranes were enrolled for further meta-analysis. DATA COLLECTION AND ANALYSIS: We conducted both a descriptive analysis and a meta-analysis. In the meta-analysis, we utilized the Mantel-Haenszel random effects model to analyze dichotomous data, employing the relative risk (RR) as the effect measure along with 95% confidence intervals (CIs). The study quality was evaluated using Cochrane Collaboration's risk of bias assessment tool (RoB 2). A random-effects model was applied for the meta-analysis. MAIN RESULTS: After screening 3303 articles from five databases, a total of nine randomized controlled studies composed of 1071 patients were included. Our analysis included 534 patients in the PGE2 group and 537 patients in the oxytocin group. The pooled estimate of vaginal deliveries following PGE2 induction stood at 84.2%, while after oxytocin induction, it was 79.8%. The meta-analysis showed no statistical difference between the two groups in terms of the rate of vaginal delivery (pooled RR, 1.05; 95% CI: 0.95-1.16; P value for Q, 0.001; I2 , 71.14%), cesarean section (pooled RR, 0.84; 95% CI: 0.52-1.35; P value for Q, 0.007; I2 , 61.69%) and induction-delivery interval (pooled standard mean difference, 0.09; 95% CI: -0.67 to 0.85; P value for Q, 0.000; I2 , 96.45%). Since the results for fetal distress and uterine hyperstimulation were consistent across all enrolled studies, no further meta-analysis was conducted. CONCLUSIONS: When amalgamating the available literature, it implies that oxytocin was found to have similar effects as PGE2 on delivery outcomes and safety concerns in pregnant women with GA ≥36 weeks. Although the uterine cervix was unfavorable, both low and high doses of oxytocin were feasible for IOL.

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types.

BACKGROUND: The COP9 signalosome subunit 6 (COPS6) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM: To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS: We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer. RESULTS: Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types. Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases. Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation. Additionally, positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer. Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in certain types of cancer. The correlation between COPS6 expression level and cancer-associated fibroblast infiltration exhibited heterogeneity, in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor, and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma. The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type. Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level. These genes were predominantly involved in processes, such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection. CONCLUSION: In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

Hemorrhagic Bartholin's cyst in a woman using anti-platelet medication: A case report and review of the literature.

BACKGROUND: We report the case of a postmenopausal female with a hemorrhagic Bartholin's cyst who has been using an antiplatelet medication. CASE SUMMARY: A postmenopausal woman, 84 years of age, had a medical history of hypertension, diabetes mellitus, coronary artery disease (three-vessel disease), chronic kidney disease (stage 3), and dementia. The patient has been taking clopidogrel, an antiplatelet medication, for several years. She presented at our outpatient clinic complaining of painful swelling over her left vulva for several days. A Bartholin's cyst over the left vulva was suspected, and the patient underwent marsupialization under local anesthesia, which was well-tolerated. During the incision procedure, bright-red blood with some blood clots was discharged, and a hemorrhagic Bartholin's cyst was observed. There was no recurrence of the hemorrhagic Bartholin's cyst during the 6-mo subsequent follow-up period. CONCLUSION: Hemorrhagic Bartholin's cysts rarely occur. We report the case of a postmenopausal female with a hemorrhagic Bartholin's cyst who had been on antiplatelets and was successfully treated with marsupialization. No recurrence was noted during the 6-mo follow-up period. Older females taking antiplatelets should be cautious of bleeding when presenting with a Bartholin's cyst.

Extensive genetic diversity of severe fever with thrombocytopenia syndrome virus circulating in Hubei Province, China, 2018-2022.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The clinical disease characteristics and case fatality rates of SFTSV may vary across distinct regions and among different variant genotypes. From 2018 to 2022, we surveyed and recruited 202 severe fever with thrombocytopenia syndrome (SFTS) patients in Hubei Province, a high-incidence area of the epidemic, and conducted timely and systematic research on the disease characteristics, SFTSV diversity, and the correlation between virus genome variation and clinical diseases. Our study identified at least 6 genotypes of SFTSV prevalent in Hubei Province based on the analysis of the S, M, and L genome sequences of 88 virus strains. Strikingly, the dominant genotype of SFTSV was found to change during the years, indicating a dynamic shift in viral genetic diversity in the region. Phylogenetic analysis revealed the genetic exchange of Hubei SFTSV strains was relatively frequent, including 3 reassortment strains and 8 recombination strains. Despite the limited sample size, SFTSV C1 genotype may be associated with higher mortality compared to the other four genotypes, and the serum amyloid A (SAA) level, an inflammatory biomarker, was significantly elevated in these patients. Overall, our data summarize the disease characteristics of SFTSV in Hubei Province, highlight the profound changes in viral genetic diversity, and indicate the need for in-depth monitoring and exploration of the relationship between viral mutations and disease severity.

Patterns of genetic variation and morphology support the recognition of five species in the Gaultheria leucocarpa Blume (Ericaceae) group from mainland China.

Gaultheria leucocarpa and its varieties form a clade of aromatic shrubs that is widely distributed in subtropical and East Asian tropical regions. The group is taxonomically difficult and in need of thorough taxonomic investigation. This study focused on taxonomic delimitation within the G. leucocarpa group from mainland China. Field surveys covering the distributional range of G. leucocarpa in mainland China were conducted, wherein four populations from Yunnan and one from Hunan were found bearing morphological and habitat differences. A 63-species phylogenetic tree of Gaultheria based on one nuclear and three chloroplast markers that included samples from the G. leucocarpa group was reconstructed with maximum likelihood to clarify the monophyly of the G. leucocarpa group. Taxonomic relationships among populations were investigated with morphology and population genetics, the latter by using two chloroplast genes and two low-copy nuclear genes. Based on the sum of morphological and genetic analyses, we described three species of Gaultheria as new to science, clarified the taxonomic status of G. leucocarpa var. pingbienensis, elevating it to the species level, and resurrected G. crenulata and treated the varieties G. leucocarpa var. crenulata, and G. leucocarpa var. yunnanensis as synonyms of this species. We provide a key to the five species now recognized, along with descriptions and photographs.

The impact of the duration of the integrated disease management program on COPD-related outcomes.

BACKGROUND: The aim of this study is to assess the impact of the duration of the integrated disease management (IDM) program on COPD-related outcomes in real-world setting. METHODS: A retrospective cohort study among 3771 patients with COPD who had regularly completed 4 visits of IDM program within 1 year between April 1, 2017 and December 31, 2018. CAT score as the primary outcome used to investigate the association between IDM intervention duration and improvement in CAT score. Change in CAT score from baseline to each follow-up visit determined by using least-squares means (LSMeans) approach. The cut-off value of IDM duration for improving the CAT score was determined by the Youden index. Logistic regression was used to analyze the relationship between IDM intervention duration and MCID (the minimal clinically important difference) improvement in CAT score and the factor associated CAT improvement. Risks of COPD exacerbation events (COPD-related ED visit and COPD-related hospitalization) were estimated by using the cumulative incidence curve and Cox proportional hazards models. RESULT: Among 3771 enrolled COPD patients, the majority of the study cohort were males (91.51%) and 42.7% of patients had CAT score of ≥ 10 at baseline. The mean of age was 71.47 years and the mean CAT at baseline were 10.49. The mean change from baseline in CAT score was - 0.87, - 1.19, - 1.23 and - 1.40 at 3-, 6-, 9- and 12 month follow-up (p < 0.0001 for all visits), respectively. Statistically significantly lower likelihood of achieving MCID improvement in CAT were observed at 3- and 6 month compared to 9 month (at 3 month: OR: 0.720, 95% CI 0.655-0.791; at 6 month: OR: 0.905, 95% CI 0.825-0.922). And only a modest increase likelihood of achieving MCID improvement in CAT at 12 month (OR: 1.097, 95% CI 1.001-1.201) compared with 9-month follow-up. In logistic regression on the entire cohort, CAT MCID improvement was most associated with baseline CAT scores ≥ 10, followed by frequent exacerbation in previous year (> 2 episodes/year), wheezing, and GOLD B or D at baseline. In baseline CAT ≥ 10 group, patients were more likely to achieve CAT MCID improvement and had greater decreases from baseline in CAT score observed at 3-, 6-, 9-, and 12 month compared with baseline CAT score < 10 group (all p < 0.0001). Moreover, in CAT ≥ 10 groups, patients who achieved CAT MCID improvement had lower risk of subsequent COPD exacerbation events (COPD-related ED visit: aHR: 1.196, 95% CI 0.985-1.453, p = 0.0713; COPD-related hospitalization: aHR: 1.529, 95% CI 1.215-1.924, p = 0.0003) when compared to those without. CONCLUSION: This is the first real-world study indicating the association between COPD IDM intervention duration and COPD-related outcomes. From 3 to 12 month follow-up results showed that continued improvement over time in COPD-specific health status, particularly in patients with baseline CAT score of ≥ 10. Furthermore, a reduction of the risk of subsequent COPD exacerbations were observed in patients with CAT MCID improvement.

Parthenolide Attenuates Sepsis-Induced Acute Kidney Injury in Rats by Reducing Inflammation.

Background: Sepsis is a common complication of severe trauma, burns, infection, or major surgery. This disease-related end-organ dysfunction results from systemic inflammatory response syndrome (SIRS). Acute kidney damage (AKI), also known as acute renal failure, is one of the most frequent and serious sequelae of sepsis. Nuclear transcription factor-κB (NF-κB) regulates the transcription of inflammation-related genes and operates as a mediator in the immune system. While parthenolide (PTL) has been reported to prevent harmful inflammatory reactions, its effects on sepsis-associated AKI are unknown. The current study investigates the effects of PTL in sepsis-associated AKI using cell and cecal ligation and puncture (CLP) models. Methods: Lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells were treated with 10 µM PTL. Inflammatory mediators, including TNF-α, IL-6, and IL-1ß, in the culture supernatants were measured by ELISA, and NF-κB levels were assessed by qPCR. After the generation of the septic CLP model, rats were intraperitoneally injected with 500 g/kg PTL and were euthanized after 72 h. Serum and kidney samples were analyzed. Results: TNF-α, IL-1ß, and IL-6 levels were elevated after LPS treatment of rat glomerular mesangial cells (p=0.004, p=0.002, and p=0.004, respectively) but were significantly reduced in the PTL treatment group (p ≤ 0.001, p=0.01, and p ≤ 0.001). NF-κB p65 levels were also increased after LPS treatment in this group and were reduced in the PTL treatment group. PTL treatment also reduced kidney damage after CLP induction, as shown by histological analysis and reductions in the levels of BUN, Cre, KIM-1, and NAGL. CLP-induced kidney inflammation together with increased levels of proinflammatory cytokines and inflammatory-related proteins. The elevated levels of renal TNF-α, IL-6, and IL-1ß were downregulated after PTL treatment. The PTL treatment also reduced the CLP-induced activation of NF-κB p65 in the damaged kidneys. Conclusion: PTL reduced inflammation induced by CLP-induced AKI in rat models and LPS-induced damage to glomerular mesangial cells by suppressing NF-κB signaling.

A Poling-Free Supramolecular Crown Ether Compound with Large Piezoelectricity.

Supramolecular host-guest ferroelectrics based on solution processing are highly desirable because they are generally created with intrinsic piezoelectricity/ferroelectricity and do not need further poling. Poly(vinylidene fluoride) (PVDF) in the electric-active beta phase after stretching/annealing still shows no piezoelectric response unless poled. Although many supramolecular host-guest ferroelectrics have been discovered, their piezoelectricity is relatively small. Based on H/F substitution, we reported a supramolecular host-guest compound [(CF3-C6H4-NH3)(18-crown-6)][TFSA] (CF3-C6H4-NH3 = 4-trifluoromethylanilinium, TFSA = bis(trifluoromethanesulfonyl)ammonium) with a remarkable piezoelectric response of 42 pC/N under no poling condition. The introduction of F atoms increases phase transition temperature, polar axes, second harmonic generation (SHG) intensity, and piezoelectric coefficient d33. To our knowledge, such a large piezoelectric performance of [(CF3-C6H4-NH3)(18-crown-6)][TFSA] makes its d33, piezoelectric voltage coefficient g33, and mechanical quality factor Qm the highest among the reported supramolecular host-guest ferroelectric compounds and even larger than the values of PVDF. This work provides inspiration for optimizing piezoelectricity on molecular materials.

The association between paraspinal muscle degeneration and osteoporotic vertebral compression fracture severity in postmenopausal women.

BACKGROUND: According to reports in the literature, osteoporotic vertebral compression fracture (OVCF) is associated with paraspinal muscle degeneration; however, the association between the severity of OVCF and paraspinal muscle degeneration is not clear. OBJECTIVE: The purpose of this study was to investigate the association between paraspinal muscle degeneration and OVCF severity in postmenopausal women. METHODS: Three hundred and seventy-six MRI images from 47 patients were collected and analyzed. Sagittal and axial coronal T2-weighted images were used to measure the fractured vertebra sagittal cross-sectional area (FSCSA), the adjacent normal vertebral body sagittal cross-sectional area (NSCSA), paraspinal muscle cross-sectional area (CSA), and the fat cross-sectional area (FCSA). The ratio of fractured vertebra compressed sagittal cross-sectional area (RCSA) and fatty infiltration ratio (FIR) was subsequently calculated. The formulas for RCSA and FIR calculations are as follows: RCSA = (NSCSA-FSCSA)/NSCSA; FIR = FCSA/CSA. RCSA and FIR represent the severity of OVCF and paraspinal muscle degeneration, respectively. RESULTS: The correlation between paraspinal muscle degeneration and OVCF severity was analyzed using the Pearson correlation, and multiple regression analysis was performed to explore related risk factors. OVCF severity was closely associated with paraspinal muscle degeneration (L3/4 FIR r= 0.704, P< 0.05; L4/5 FIR r= 0.578, P< 0.05; L5/S1 FIR r= 0.581, P< 0.05). Multiple regression analysis demonstrated that the risk factor for OVCF severity was L3/4 FIR (ß= 0.421, P= 0.033). CONCLUSION: OVCF severity was associated with the FIR of paraspinal muscles, and L3/4 FIR was a predictive factor for OVCF severity in postmenopausal women.

Prognostic Value of Systemic Immune-Inflammation Index (SII) in Patients with Glioblastoma: A Comprehensive Study Based on Meta-Analysis and Retrospective Single-Center Analysis.

Inflammation is related to cancer. The systemic immune-inflammation index (SII) has been linked to the prognosis of many types of cancer. The present study aimed to determine the prognostic value of the SII in glioblastoma (GBM) patients based on meta-analysis and single-center retrospective analysis. Relevant publications published before 1 October 2022 were identified by searching PubMed, EMBASE, Cochrane Library databases, and Web of Science. Moreover, 208 GBM patients from Zhongnan Hospital were incorporated. Kaplan−Meier and Cox regression analyses determined the prognostic significance of inflammatory markers. By combining these indicators, we developed scoring systems. Nomograms were also built by incorporating independent variables. The accuracies of nomograms were evaluated by Harrell's concordance index (c-index) and the calibration curve. According to meta-analysis, an elevated SII predicted the worst overall survival (OS) (Hazard ratio [HR] = 1.87, p < 0.001). Furthermore, a higher SII (>510.8) (HR = 1.782, p = 0.007) also predicted a poorer outcome in a retrospective cohort. The scoring systems of SII-NLR (neutrophil-to-lymphocyte ratio) showed the best predictive power for OS. The nomogram without MGMT (c-index = 0.843) exhibited a similar accuracy to that with MGMT (c-index = 0.848). A pre-treatment SII is independently associated with OS in GBM. A nomogram integrating the SII-NLR score may facilitate a comprehensive survival evaluation independent of molecular tests in GBM.

Blood monocyte levels predict the risk of acute exacerbations of chronic obstructive pulmonary disease: a retrospective case-control study.

Monocytes were critical cells in the innate immune system. Monocyte recruitment to the lungs is a crucial process of pathophysiology in chronic obstructive pulmonary disease (COPD). Current evidence on the association between the occurrence of acute exacerbations of COPD (AECOPD) and monocytes was unclear. This study aimed to examine whether blood monocytes are associated with the occurrence of AECOPD and to determine the specific blood monocyte level to predict AECOPD. A retrospective case-control study was conducted at Changhua Christian Hospital. A total of 444 eligible patients with COPD were included between January 2017 and December 2019. Restricted cubic splines were used to analyze the nonlinear relationships between continuous white blood cell values and the occurrence of AECOPD. The association between monocytes and the occurrence of AECOPD was assessed using the logistic, lasso, and ridge regression models. Restricted cubic splines revealed nonlinear associations among the monocyte level, the continuous value of the eosinophil-to-lymphocyte ratio, and the occurrence of AECOPD. The lowest risk of occurrence of AECOPD ranged from 7.4 to 10%; < 7.4% with an absolute count < 0.62 or > 10% indicated significant risk. No significant association was noted between the eosinophil-to-lymphocyte ratio categories in the tertiles (< 0.049, 0.049 to < 0.122, and ≥ 0.122) and the risk of AECOPD. A significantly higher risk was noted in the association of the occurrence of AECOPD with the CAT score; mMRC score; wheezing cough; preexisting chronic pulmonary disease; hypertension and malignancy; use of dual- and triple, and oral long-acting bronchodilators for COPD treatment; and WBC count. We reported a nonlinear relationship between monocytes and the occurrence of AECOPD. Patients with monocyte percentage of > 10% or < 7.4% with an absolute count < 0.62 had higher risk of occurrence of AECOPD. Overall, our study demonstrated the specific value of monocytes in identifying high risks of the occurrence of AECOPD; this value is an easy-to-obtain, inexpensive biomarker in patients with AECOPD and should be further investigated in future prospective clinical studies.

The First Chiro-Inositol Organosilicon Ferroelectric Crystal.

Organosilicons have been used extensively in aerospace, electronics, food, medicine and other fields, due to their low viscosity, hydrophobicity, corrosion resistance, non-toxic, and physiologically inert features. Despite extensive interest, however, organosilicon ferroelectric crystals have never been found. Here, by using the chemical design strategy, we successfully obtained a molecular ferroelectric D-chiro-inositol-SiMe3 with polar P43 symmetry, whose spontaneous polarization can be electrically switchable on thin film. The introduction of organosilicon groups endows the thin films with excellent softness, ductility and flexibility (extremely low hardness of 72.8 MPa and small elastic modulus of 5.04 GPa) that are desirable for biomedical and human-compatible applications. As the first case of organosilicon ferroelectric crystal to date, this work offers a new structural paradigm for molecular ferroelectrics, and highlights their potential for flexible bio-electronic applications.

Assistive Mobility Control of a Robotic Hip-Knee Exoskeleton for Gait Training.

In this paper, we present an assistive mobility control for a robotic hip-knee exoskeleton intended for gait training. The robotic hip-knee exoskeleton is designed with an active flexion/extension and a passive abduction/adduction at each hip joint and an active flexion/extension at each knee joint to comply with the movement of lower limbs. While facilitating walking with the robotic exoskeleton, model-free linear extended state observer (LESO)-based controllers are proposed for gait control, in which the LESO is used to deal with each user's different lower limb parameters and unknown exerted torques. Walking and ascending experiments were conducted to evaluate the performance of the proposed methods, and the results are shown with respect to walking parameters. Moreover, a preliminary study for an extended application to the recovery of normal gaits that relieves the freezing of gait (FOG) in Parkinson's disease (PD) patients is also investigated in the paper.

The Mediating Effect of Cytokines on the Association between Fungal Sensitization and Poor Clinical Outcome in Asthma.

Sensitization to fungal allergens is one of the proposed phenotypes in asthma. An association between fungal sensitization and worse clinical outcomes is apparent. Moreover, fungal sensitization in asthma that is associated with different type of immunological mechanism has been reported. How the role of cytokines mediates the association between fungal sensitization and poorer asthmatic outcomes remains unclear. We aimed to determine role of cytokines in the relationship between fungal sensitization and worse clinical outcomes in asthma. METHOD: We conducted a prospective study to recruit adult patients with asthma. Data including age, sex, height, weight, smoking history, medication, emergency visit and admission, pulmonary function testing result, and Asthma Control Test (ACT) scores were collected. We used the automated BioIC method to measure fungal allergen sIgE in sera. Serum levels of Interleukin (IL) -4, IL-13, IL-6, IL-9, IL-10, IL-17 A, IL-22, Interferon (IFN) -γ, Immunoglobulin E (IgE), Tumor necrosis factor-α (TNF-α), and Transforming growth factor-ß (TGF-ß) were measured using ELISA. RESULT: IL-6 and IL-17A had a significant positive correlation between sensitization and most fungi species compared to IgE. Sensitization to Candida albicans had strongly positive association both with IL-6 and IL-17A. However, only IL-17A had significant relationship with ED visit times. The mediation analysis result indicates that IL-17A had a significant positively mediating effect (ME) on the association between Candida albicans and ED visit times. CONCLUSION: IL-17A is a potential mediator to link Candida albicans sensitization and ED visits for asthma. We suggest that patients with fungal sensitization, such as Candida albicans, have poorer outcomes associated with Th17-mediated immune response rather than Th2.

Cumulative Scoring Systems and Nomograms for Predicating Survival in Patients With Glioblastomas: A Study Based on Peripheral Inflammatory Markers.

Inflammation is a hallmark of cancers. The purpose of the present study was to evaluate the prognostic potential of hematological inflammatory markers in glioblastoma multiforme (GBM) patients. The clinical data of 99 patients with lower-grade gliomas and 88 patients with GBMs were retrospectively analyzed. The optimal cutoff values for peripheral markers were determined by X-tile. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify markers with prognostic significance. Several scoring systems were constructed by combining these prognostic markers. The predictive accuracies of nomograms incorporating these scoring systems were evaluated by Harrell's concordance index and receiver operating characteristic curve analysis. GBM patients exhibited higher neutrophil counts (p=0.001), neutrophil-to-lymphocyte ratio (NLR) (p<0.001), and platelet-to-lymphocyte ratio (PLR) (p=0.001), as well as lower lymphocyte counts (p=0.023), lymphocyte-to-monocyte ratio (LMR) (p=0.015), and albumin-to-globulin ratio (AGR) (p=0.003) than those with lower-grade gliomas. Multivariate analysis indicated that a high NLR (> 2.0) (Hazard ratio[HR]=2.519, 95% confidence interval (CI): 1.220-5.204, p=0.013), low LMR (< 2.3) (HR=2.268, 95%CI: 1.172-4.386, p=0.015), or low AGR (< 1.7) (HR=2.924, 95%CI: 1.389-6.135, p=0.005) were associated with poor overall survival in GBM patients. The scoring systems of AGR-NLR, AGR-LMR, and LMR-NLR were associated with GBM survival. The nomogram integrating AGR-NLR score had the best efficacy in predicting GBM survival (c-index=0.874). Pretreatment scores of AGR-NLR, AGR-LMR, and LMR-NLR may serve as prognostic factors for GBM patients, and a nomogram integrating AGR-NLR may provide a reliable tool to facilitate personalized preoperative evaluations.

[(Histamine)(18-crown-6)2][BF4]2 is a high-temperature piezoelectric.

We discovered that [(histamine)(18-crown-6)2][BF4]2 is a high-temperature host-guest inclusion complex that presents decent piezoelectric properties (d33 = 5 pC/N), undergoes a phase transition at 406 K, and also possesses potential ferroelectricity. This work provides a new idea for constructing host-guest inclusion piezoelectrics.

Explainable Machine Learning Model for Predicting First-Time Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level. METHODS: We conducted a retrospective case-control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model's decisions. RESULTS: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745-0.921] and AUC = 0.836 [95% CI 0.757-0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was <0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD. CONCLUSIONS: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model's decision-making process.

Effectiveness of Nationwide COPD Pay-for-Performance Program on COPD Exacerbations in Taiwan.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has also imposed a substantial economic and social burden on the health care system. In Taiwan, a nationwide COPD pay-for-performance (P4P) program was designed to improve the quality of COPD-related care by introducing financial incentives for health care providers and employing a multidisciplinary team to deliver guideline-based, integrated care for patients with COPD, reducing adverse outcomes, especially COPD exacerbation. However, the results of a survey of the effectiveness of the pay-for-performance program in COPD management were inconclusive. To address this knowledge gap, this study evaluated the effectiveness of the COPD P4P program in Taiwan. METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance claims database and nationwide COPD P4P enrollment program records from June 2016 to December 2018. Patients with COPD were classified into P4P and non-P4P groups. Patients in the P4P group were matched at a ratio of 1:1 based on age, gender, region, accreditation level, Charlson Comorbidity Index (CCI), and inhaled medication prescription type to create the non-P4P group. A difference-in-difference analysis was used to evaluate the influence of the P4P program on the likelihood of COPD exacerbation, namely COPD-related emergency department (ED) visit, intensive care unit (ICU) admission, or hospitalization. RESULTS: The final sample of 14,288 patients comprised 7144 in each of the P4P and non-P4P groups. The prevalence of COPD-related ED visits, ICU admissions, and hospitalizations was higher in the P4P group than in the non-P4P group 1 year before enrollment. After enrollment, the P4P group exhibited a greater decrease in the prevalence of COPD-related ED visits and hospitalizations than the non-P4P group (ED visit: -2.98%, p<0.05, 95% confidence interval [CI]: -0.277 to -0.086; hospitalization: -1.62%, p<0.05, 95% CI: -0.232 to -0.020), whereas no significant difference was observed between the groups in terms of the changes in the prevalence of COPD-related ICU admissions. CONCLUSION: The COPD P4P program exerted a positive net effect on reducing the likelihood of COPD exacerbation, namely COPD-related ED visits and hospitalizations. Future studies should examine the long-term cost-effectiveness of the COPD P4P program.