The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer.

BACKGROUND: Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM: This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS: This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS: The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS: The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS: GOV: NCT05574998.

Reporting of Ethical Considerations in Qualitative Research Utilizing Social Media Data on Public Health Care: Scoping Review.

BACKGROUND: The internet community has become a significant source for researchers to conduct qualitative studies analyzing users' views, attitudes, and experiences about public health. However, few studies have assessed the ethical issues in qualitative research using social media data. OBJECTIVE: This study aims to review the reportage of ethical considerations in qualitative research utilizing social media data on public health care. METHODS: We performed a scoping review of studies mining text from internet communities and published in peer-reviewed journals from 2010 to May 31, 2023. These studies, limited to the English language, were retrieved to evaluate the rates of reporting ethical approval, informed consent, and privacy issues. We searched 5 databases, that is, PubMed, Web of Science, CINAHL, Cochrane, and Embase. Gray literature was supplemented from Google Scholar and OpenGrey websites. Studies using qualitative methods mining text from the internet community focusing on health care topics were deemed eligible. Data extraction was performed using a standardized data extraction spreadsheet. Findings were reported using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. RESULTS: After 4674 titles, abstracts, and full texts were screened, 108 studies on mining text from the internet community were included. Nearly half of the studies were published in the United States, with more studies from 2019 to 2022. Only 59.3% (64/108) of the studies sought ethical approval, 45.3% (49/108) mentioned informed consent, and only 12.9% (14/108) of the studies explicitly obtained informed consent. Approximately 86% (12/14) of the studies that reported informed consent obtained digital informed consent from participants/administrators, while 14% (2/14) did not describe the method used to obtain informed consent. Notably, 70.3% (76/108) of the studies contained users' written content or posts: 68% (52/76) contained verbatim quotes, while 32% (24/76) paraphrased the quotes to prevent traceability. However, 16% (4/24) of the studies that paraphrased the quotes did not report the paraphrasing methods. Moreover, 18.5% (20/108) of the studies used aggregated data analysis to protect users' privacy. Furthermore, the rates of reporting ethical approval were different between different countries (P=.02) and between papers that contained users' written content (both direct and paraphrased quotes) and papers that did not contain users' written content (P<.001). CONCLUSIONS: Our scoping review demonstrates that the reporting of ethical considerations is widely neglected in qualitative research studies using social media data; such studies should be more cautious in citing user quotes to maintain user privacy. Further, our review reveals the need for detailed information on the precautions of obtaining informed consent and paraphrasing to reduce the potential bias. A national consensus of ethical considerations such as ethical approval, informed consent, and privacy issues is needed for qualitative research of health care using social media data of internet communities.

The effects of clinical learning environment and career adaptability on resilience: A mediating analysis based on a survey of nursing interns.

BACKGROUND: The resilience education of intern nursing students has significant implications for the development and improvement of the nursing workforce. The clinical internship period is a critical time for enhancing resilience. AIMS: To evaluate the resilience level of Chinese nursing interns and explore the effects of factors affecting resilience early in their careers, focusing on the mediating roles of career adaptability between clinical learning environment and resilience. METHODS: The cross-sectional study design was adopted. From March 2022 to May 2023, 512 nursing interns in tertiary care hospitals were surveyed online with the Connor-Davidson Resilience Scale, the Clinical Learning Environment Scale for Nurse and the Career Adapt-Abilities Scale. Structural equation modelling was used to clarify the relationships among these factors. Indirect effects were tested using bootstrapped confidence intervals. RESULTS: The nursing interns showed a moderately high level of resilience [M (SD) = 70.15 (19.90)]. Gender, scholastic attainment, scholarship, career adaptability and clinical learning environment were influencing factors of nursing interns' resilience. Male interns with good academic performance showed higher levels of resilience. Career adaptability and clinical learning environment positively and directly affected their resilience level (ß = 0.62, 0.18, respectively, p < .01). Career adaptability was also positively affected by the clinical learning environment (ß = 0.36, p < .01), and mediated the effect of clinical learning environment on resilience (ß = 0.22, p < .01). CONCLUSION: Clinical learning environment can positively affect the resilience level of nursing interns. Career adaptability can affect resilience directly and also play a mediating role between clinical learning environment and resilience. Thus, promotion of career adaptability and clinical teaching environment should be the potential strategies for nursing interns to improve their resilience, especially for female nursing interns with low academic performance.

Pre-treatment assessment of chemotherapy for cancer patients: a multi-site evidence implementation project of 74 hospitals in China.

BACKGROUND: Chemotherapy, whilst treating tumours, can also lead to numerous adverse reactions such as nausea and vomiting, fatigue and kidney toxicity, threatening the physical and mental health of patients. Simultaneously, misuse of chemotherapeutic drugs can seriously endanger patients' lives. Therefore, to maintain the safety of chemotherapy for cancer patients and to reduce the incidence of adverse reactions to chemotherapy, many guidelines state that a comprehensive assessment of the cancer patient should be conducted and documented before chemotherapy. This recommended procedure, however, has yet to be extensively embraced in Chinese hospitals. As such, this study aimed to standardise the content of pre-chemotherapy assessment for cancer patients in hospitals and to improve nurses' adherence to pre-chemotherapy assessment of cancer patients by conducting a national multi-site evidence implementation in China, hence protecting the safety of cancer patients undergoing chemotherapy and reducing the incidence of adverse reactions to chemotherapy in patients. METHODS: The national multi-site evidence implementation project was launched by a JBI Centre of Excellence in China and conducted using the JBI approach to evidence implementation. A pre- and post-audit approach was used to evaluate the effectiveness of the project. This project had seven phases: training, planning, baseline audit, evidence implementation, two rounds of follow-up audits (3 and 9 months after evidence implementation, respectively) and sustainability assessment. A live online broadcast allowed all participating hospitals to come together to provide a summary and feedback on the implementation of the project. RESULTS: Seventy-four hospitals from 32 cities in China participated in the project, four withdrew during the project's implementation, and 70 hospitals completed the project. The pre-and post-audit showed a significant improvement in the compliance rate of nurses performing pre-chemotherapy assessments for cancer patients. Patient satisfaction and chemotherapy safety were also improved through the project's implementation, and the participating nurses' enthusiasm and belief in implementing evidence into practice was increased. CONCLUSION: The study demonstrated the feasibility of academic centres working with hospitals to promote the dissemination of evidence in clinical practice to accelerate knowledge translation. Further research is needed on the effectiveness of cross-regional and cross-organisational collaborations to facilitate evidence dissemination.

Two novel compound heterozygous variants of the GCDH gene in two Chinese families with glutaric acidaemia type I identified by high-throughput sequencing and a literature review.

Autosomal recessive glutaric acidaemia type I (GA-I) is a rare hereditary metabolic disease characterized by increased organic acids and neurologic symptoms. Although numerous variants in the GCDH gene have been identified to be connected with the pathogenesis of GA-I, the relationship between genotype and phenotype remains uncertain. In this study, we evaluated genetic data for two GA-I patients from Hubei, China, and we reviewed the previous research findings to clarify the genetic heterogeneity of GA-I and identify the potential causative variants. After we extracted genomic DNA from peripheral blood samples obtained from two unrelated Chinese families, we used target capture high-throughput sequencing combined with Sanger sequencing to determine likely pathogenic variants in the two probands. Electronic databases were also searched for the literature review. The genetic analysis revealed two compound heterozygous variants in the GCDH gene expected to lead to GA-I in the two probands (P1 and P2), with P1 carrying two known variants (c.892G > A/p. A298T and c.1244-2A > C/IVS10-2A > C) and P2 harbouring two novel variants (c.370G > T/p.G124W and c.473A > G/p.E158G). In the literature review, the most common alleles in low excretors (i.e., individuals with low excretion of GA) were R227P, V400M, M405V, and A298T, with variation in the severity of clinical phenotypes. Overall, we identified two novel GCDH gene candidate pathogenic variants in a Chinese patient, enriching the GCDH gene mutational spectrum and providing a solid foundation for the early diagnosis of GA-I patients with low excretion.

Sulforaphane inhibits TGF-ß-induced fibrogenesis and inflammation in human Tenon's fibroblasts.

Purpose: Subconjunctival fibrosis is the main cause of failure after glaucoma filtration surgery. We explored the effects of sulforaphane (SFN) on the conversion of human Tenon's fibroblasts (HTFs) into myofibroblasts, transforming growth factor (TGF)-ß-induced contraction of collagen gel, and inflammation. Methods: After treatment with the combination of TGF-ß and SFN or TGF-ß alone, primary HTFs were subjected to a three-dimensional collagen contraction experiment to examine their contractility. Levels of α smooth muscle actin (α-SMA), synthesis of extracellular matrix (ECM), and phosphorylation of various signaling molecules were determined by western blot or quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Fluorescence microscopy was employed to examine stress fiber formation in HTFs. The expressions of interleukin (IL)-6, IL-8, and connective tissue growth factor (CTGF) were determined using RT-qPCR. Results: The contraction of myofibroblasts caused by TGF-ß was significantly suppressed by SFN. This suppressive effect was exerted via the differentiation of HTFs into myofibroblasts by inhibiting the production of fibronectin and the expression of α-SMA. Moreover, SFN treatment reduced the expression of TGF-ß-promoted integrins ß1 and α5, myosin light chain (MLC) phosphorylation, and stress fiber formation, as well as the expression of IL-6, IL-8, and CTGF. Finally, TGF-ß-induced Smad2/3 and extracellular signal-regulated kinase (ERK) phosphorylations were attenuated by SFN. Conclusions: SFN inhibits HTF contractility, differentiation into myofibroblasts, and inflammation caused by TGF-ß. These effects are mediated by both classic and non-classic signaling pathways. Our results indicate that SFN has potent anti-fibrotic and anti-inflammatory effects in HTFs and is a potential candidate for subconjunctival fibrosis therapy.

Flexible and accurate total variation and cascaded denoisers-based image reconstruction algorithm for hyperspectrally compressed ultrafast photography.

Hyperspectrally compressed ultrafast photography (HCUP) based on compressed sensing and time- and spectrum-to-space mappings can simultaneously realize the temporal and spectral imaging of non-repeatable or difficult-to-repeat transient events with a passive manner in single exposure. HCUP possesses an incredibly high frame rate of tens of trillions of frames per second and a sequence depth of several hundred, and therefore plays a revolutionary role in single-shot ultrafast optical imaging. However, due to ultra-high data compression ratios induced by the extremely large sequence depth, as well as limited fidelities of traditional algorithms over the image reconstruction process, HCUP suffers from a poor image reconstruction quality and fails to capture fine structures in complex transient scenes. To overcome these restrictions, we report a flexible image reconstruction algorithm based on a total variation (TV) and cascaded denoisers (CD) for HCUP, named the TV-CD algorithm. The TV-CD algorithm applies the TV denoising model cascaded with several advanced deep learning-based denoising models in the iterative plug-and-play alternating direction method of multipliers framework, which not only preserves the image smoothness with TV, but also obtains more priori with CD. Therefore, it solves the common sparsity representation problem in local similarity and motion compensation. Both the simulation and experimental results show that the proposed TV-CD algorithm can effectively improve the image reconstruction accuracy and quality of HCUP, and may further promote the practical applications of HCUP in capturing high-dimensional complex physical, chemical and biological ultrafast dynamic scenes.

Luteolin ameliorates cornea stromal collagen degradation and inflammatory damage in rats with corneal alkali burn.

Corneal alkali burn (AB) is a blindness-causing ocular trauma commonly seen in clinics. An excessive inflammatory reaction and stromal collagen degradation contribute to corneal pathological damage. Luteolin (LUT) has been studied for its anti-inflammatory effects. In this study, the effect of LUT on cornea stromal collagen degradation and inflammatory damage in rats with corneal alkali burn was investigated. After corneal alkali burn, rats were randomly assigned to the AB group and AB + LUT group and received an injection of saline and LUT (200 mg/kg) once daily. Subsequently, corneal opacity, epithelial defects, inflammation and neovascularization (NV) were observed and recorded on Days 1, 2, 3, 7 and 14 post-injury. The concentration of LUT in ocular surface tissues and anterior chamber, as well as the levels of collagen degradation, inflammatory cytokines, matrix metalloproteinases (MMPs) and their activity in the cornea were detected. Human corneal fibroblasts (HCFs) were co-cultured with interleukin (IL)-1ß and LUT. Cell proliferation and apoptosis were assessed by CCK-8 assay and flow cytometry respectively. Measurement of hydroxyproline (HYP) in culture supernatants was used to quantify the amount of collagen degradation. Plasmin activity was also assessed. ELISA or real-time PCR was used to detect the production of matrix metalloproteinases (MMPs), IL-8, IL-6 and monocyte chemotactic protein (MCP)-1. Furthermore, the immunoblot method was used to assess the phosphorylation of mitogen-activated protein kinases (MAPKs), transforming growth factor-ß-activated kinase (TAK)-1, activator protein-1 (AP-1) and inhibitory protein IκB-α. At last, immunofluorescence staining helped to develop nuclear factor (NF)-κB. LUT was detectable in ocular tissues and anterior chamber after intraperitoneal injection. An intraperitoneal injection of LUT ameliorated alkali burn-elicited corneal opacity, corneal epithelial defects, collagen degradation, NV, and the infiltration of inflammatory cells. The mRNA expressions of IL-1ß, IL-6, MCP-1, vascular endothelial growth factor (VEGF)-A, and MMPs in corneal tissue were downregulated by LUT intervention. And its administration reduced the protein levels of IL-1ß, collagenases, and MMP activity. Furthermore, in vitro study showed that LUT inhibited IL-1ß-induced type I collagen degradation and the release of inflammatory cytokines and chemokines by corneal stromal fibroblasts. LUT also inhibited the IL-1ß-induced activation of TAK-1, mitogen-activated protein kinase (MAPK), c-Jun, and NF-κB signaling pathways in these cells. Our results demonstrate that LUT inhibited alkali burn-stimulated collagen breakdown and corneal inflammation, most likely by attenuating the IL-1ß signaling pathway. LUT may therefore prove to be of clinical value for treating corneal alkali burns.

Effect of the CYBA C242T Polymorphism on Preeclampsia Pathogenesis in the Chinese Population.

BACKGROUND: Although the mechanisms responsible for the pathogenesis of preeclampsia (PE) have not been entirely clarified, oxidative stress is thought to be its leading cause. As a major component responsible for reactive oxygen species (ROS) production during oxidative stress, p22phox, encoded by CYBA, is an essential subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The aim of this study was to investigate whether CYBA expression and its polymorphism are associated with PE. METHODS: Expression of CYBA was analysed in placentas from PE and control groups, as well as in HTR-8/SVneo cells stimulated with CoCl2 and TNF-α. Then, the CYBA C242T polymorphism in 1184 patients with PE and 1421 healthy controls was genotyped using the TaqMan probe, and the different distributions identified were confirmed by a case‒control association study. RESULTS: Expression of CYBA mRNA and protein in the placenta of pregnant women with PE was significantly increased compared to controls. Expression of CYBA mRNA was also increased in HTR-8/SVneo cells collected after 24 h of separate stimulation with cobalt chloride and TNF-α. There was no significant difference in the distribution of the C242T locus genotype and CYBA allele frequency between the case group and control group (P > 0.05). CONCLUSIONS: CYBA may play a role in the pathogenesis of oxidative stress in PE, in which it may function by cooperating with the TNF-α-related inflammatory pathway. Although no discrepant distribution of the CYBA C242T polymorphism in the Chinese population was detected, it is necessary to examine multiple CYBA SNPs in diverse populations and perform functional experiments to gain further insights into its pathogenesis.

Methods for Analyzing the Contents of Social Media for Health Care: Scoping Review.

BACKGROUND: Given the rapid development of social media, effective extraction and analysis of the contents of social media for health care have attracted widespread attention from health care providers. As far as we know, most of the reviews focus on the application of social media, and there is a lack of reviews that integrate the methods for analyzing social media information for health care. OBJECTIVE: This scoping review aims to answer the following 4 questions: (1) What types of research have been used to investigate social media for health care, (2) what methods have been used to analyze the existing health information on social media, (3) what indicators should be applied to collect and evaluate the characteristics of methods for analyzing the contents of social media for health care, and (4) what are the current problems and development directions of methods used to analyze the contents of social media for health care? METHODS: A scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. We searched PubMed, the Web of Science, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library for the period from 2010 to May 2023 for primary studies focusing on social media and health care. Two independent reviewers screened eligible studies against inclusion criteria. A narrative synthesis of the included studies was conducted. RESULTS: Of 16,161 identified citations, 134 (0.8%) studies were included in this review. These included 67 (50.0%) qualitative designs, 43 (32.1%) quantitative designs, and 24 (17.9%) mixed methods designs. The applied research methods were classified based on the following aspects: (1) manual analysis methods (content analysis methodology, grounded theory, ethnography, classification analysis, thematic analysis, and scoring tables) and computer-aided analysis methods (latent Dirichlet allocation, support vector machine, probabilistic clustering, image analysis, topic modeling, sentiment analysis, and other natural language processing technologies), (2) categories of research contents, and (3) health care areas (health practice, health services, and health education). CONCLUSIONS: Based on an extensive literature review, we investigated the methods for analyzing the contents of social media for health care to determine the main applications, differences, trends, and existing problems. We also discussed the implications for the future. Traditional content analysis is still the mainstream method for analyzing social media content, and future research may be combined with big data research. With the progress of computers, mobile phones, smartwatches, and other smart devices, social media information sources will become more diversified. Future research can combine new sources, such as pictures, videos, and physiological signals, with online social networking to adapt to the development trend of the internet. More medical information talents need to be trained in the future to better solve the problem of network information analysis. Overall, this scoping review can be useful for a large audience that includes researchers entering the field.

Construction of an Emotional Lexicon of Patients With Breast Cancer: Development and Sentiment Analysis.

BACKGROUND: The innovative method of sentiment analysis based on an emotional lexicon shows prominent advantages in capturing emotional information, such as individual attitudes, experiences, and needs, which provides a new perspective and method for emotion recognition and management for patients with breast cancer (BC). However, at present, sentiment analysis in the field of BC is limited, and there is no emotional lexicon for this field. Therefore, it is necessary to construct an emotional lexicon that conforms to the characteristics of patients with BC so as to provide a new tool for accurate identification and analysis of the patients' emotions and a new method for their personalized emotion management. OBJECTIVE: This study aimed to construct an emotional lexicon of patients with BC. METHODS: Emotional words were obtained by merging the words in 2 general sentiment lexicons, the Chinese Linguistic Inquiry and Word Count (C-LIWC) and HowNet, and the words in text corpora acquired from patients with BC via Weibo, semistructured interviews, and expressive writing. The lexicon was constructed using manual annotation and classification under the guidance of Russell's valence-arousal space. Ekman's basic emotional categories, Lazarus' cognitive appraisal theory of emotion, and a qualitative text analysis based on the text corpora of patients with BC were combined to determine the fine-grained emotional categories of the lexicon we constructed. Precision, recall, and the F1-score were used to evaluate the lexicon's performance. RESULTS: The text corpora collected from patients in different stages of BC included 150 written materials, 17 interviews, and 6689 original posts and comments from Weibo, with a total of 1,923,593 Chinese characters. The emotional lexicon of patients with BC contained 9357 words and covered 8 fine-grained emotional categories: joy, anger, sadness, fear, disgust, surprise, somatic symptoms, and BC terminology. Experimental results showed that precision, recall, and the F1-score of positive emotional words were 98.42%, 99.73%, and 99.07%, respectively, and those of negative emotional words were 99.73%, 98.38%, and 99.05%, respectively, which all significantly outperformed the C-LIWC and HowNet. CONCLUSIONS: The emotional lexicon with fine-grained emotional categories conforms to the characteristics of patients with BC. Its performance related to identifying and classifying domain-specific emotional words in BC is better compared to the C-LIWC and HowNet. This lexicon not only provides a new tool for sentiment analysis in the field of BC but also provides a new perspective for recognizing the specific emotional state and needs of patients with BC and formulating tailored emotional management plans.

Psychometric testing of the Chinese National Health Service Sustainability Model as an instrument to assess innovation in Chinese nursing settings.

OBJECTIVES: To conduct psychometric testing of the Chinese version of the National Health Service Sustainability Model as an instrument to assess the sustainability of innovation in the Chinese nursing setting. BACKGROUND: Evidence-based practice is recognized worldwide as a way to improve the quality of healthcare; however, many evidence-based practice programmes decline over time and do not sustain the benefits of their improvements. A sustainability assessment tool is used internationally but its use has not been validated in China. DESIGN: A methodological study to test instrument validity and reliability. METHODS: The data collection was conducted from 15 June 2022 to 31 August 2022. The internal consistency of the Chinese version of the sustainability model was measured with Cronbach's alpha. Confirmatory factor analysis was used to test the model's structural validity. RESULTS: Four hundred eighty-three questionnaires were returned, of which 478 were valid. The short time taken to evaluate the Chinese version of the sustainability model demonstrated its efficiency and ability to adapt to a busy clinical environment. The confirmatory factor analysis showed a good fit model and supported the convergence validity of the sustainability model. The Cronbach's alpha coefficient was 0.905 for the total scale, which indicated good internal consistency. CONCLUSIONS: The results of this study suggest that the Chinese version of the sustainability model is a valid, reliable and efficient tool for measuring the sustainability of evidence-based practices in Chinese nursing settings.

Weighted multi-scale denoising via adaptive multi-channel fusion for compressed ultrafast photography.

Being capable of passively capturing transient scenes occurring in picoseconds and even shorter time with an extremely large sequence depth in a snapshot, compressed ultrafast photography (CUP) has aroused tremendous attention in ultrafast optical imaging. However, the high compression ratio induced by large sequence depth brings the problem of low image quality in image reconstruction, preventing CUP from observing transient scenes with fine spatial information. To overcome these restrictions, we propose an efficient image reconstruction algorithm with multi-scale (MS) weighted denoising based on the plug-and-play (PnP) based alternating direction method of multipliers (ADMM) framework for multi-channel coupled CUP (MC-CUP), named the MCMS-PnP algorithm. By removing non-Gaussian distributed noise using weighted MS denoising during each iteration of the ADMM, and adaptively adjusting the weights via sufficiently exploiting the coupling information among different acquisition channels collected by MC-CUP, a synergistic combination of hardware and algorithm can be realized to significantly improve the quality of image reconstruction. Both simulation and experimental results demonstrate that the proposed adaptive MCMS-PnP algorithm can effectively improve the accuracy and quality of reconstructed images in MC-CUP, and extend the detectable range of CUP to transient scenes with fine structures.

Widespread of Potential Pathogen-Derived Extracellular Vesicles Carrying Antibiotic Resistance Genes in Indoor Dust.

Extracellular vesicles (EVs) are newly recognized as important vectors for carrying and spreading antibiotic resistance genes (ARGs). However, the ARGs harbored by EVs in ambient environments and the transfer potential are still unclear. In this study, the prevalence of ARGs and mobile genetic elements (MGEs) in EVs and their microbial origins were studied in indoor dust from restaurants, kindergarten, dormitories, and vehicles. The amount of EVs ranged from 3.40 × 107 to 1.09 × 1011 particles/g dust. The length of EV-associated DNA fragments was between 21 bp and 9.7 kb. Metagenomic sequencing showed that a total of 241 antibiotic ARG subtypes encoding resistance to 16 common classes were detected in the EVs from all four fields. Multidrug, quinolone, and macrolide resistance genes were the dominant types. 15 ARG subtypes were exclusively carried and even enriched in EVs compared to the indoor microbiome. Moreover, several ARGs showed co-occurrence with MGEs. The EVs showed distinct taxonomic composition with their original dust microbiota. 30.23% of EV-associated DNA was predicted to originate from potential pathogens. Our results indicated the widespread of EVs carrying ARGs and virulence genes in daily life indoor dust, provided new insights into the status of extracellular DNA, and raised risk concerns on their gene transfer potential.

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to explore the safety profile of trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical data. METHODS: We explored trastuzumab deruxtecan related adverse events (AEs) in clinical trials available in ClinicalTrials.gov and electronic databases (MEDLINE, EMBASE and PubMed) up to July 16, 2022. Meta-analysis was performed by using incidence rate with 95%CIs. In the pharmacovigilance study of FDA Adverse Event Reporting System (FAERS), the reporting odds ratio (ROR) and the medicines and healthcare products regulatory agency (MHRA) methods were used to analyse the real-world AEs (up to June 28, 2022). RESULTS AND DISCUSSION: A 8 clinical trials enrolled 1457 patients were included. The most common AEs of any grade were gastrointestinal disorders and blood and lymphatic system disorders. The most common AE of grade 3 or higher was neutropenia (21.4%, 95%CI: 14.7%-28.1%, I2  = 91%). The incidence of interstitial lung disease (ILD) and decreased left ventricular ejection fraction were 10.9% (95%CI: 7.2%-14.5%, I2  = 82%) and 1.2% (95%CI: 0.7%-2.2%, I2  = 98%), respectively. A total of 1244 AE reports were identified in the pharmacovigilance study. Gastrointestinal toxicity (ROR = 21.65), myelosuppression (ROR = 36.88), interstitial lung disease (ROR = 50.30), pneumonitis (ROR = 36.59), decreased ejection fraction (ROR = 16.08), and taste disorder (ROR = 14.06) mentioned in the instructions showed strong signals. Also, ascites (ROR = 14.90), lung opacity (ROR = 78.80), pulmonary fibrosis (ROR = 5.59), and increased KL-6 (ROR = 1761.97), which were not mentioned in the instructions, showed strong signals. WHAT IS NEW AND CONCLUSION: Trastuzumab deruxtecan was well tolerated, and more attention should be paid on ILD as well as decreased ejection fraction.

iATC-NRAKEL: an efficient multi-label classifier for recognizing anatomical therapeutic chemical classes of drugs.

MOTIVATION: The anatomical therapeutic chemical (ATC) classification system plays an increasingly important role in drug repositioning and discovery. The correct identification of classes in each level of such system that a given drug may belong to is an essential problem. Several multi-label classifiers have been proposed in this regard. Although they provided satisfactory performance, the feature extraction procedures were still rough. More refined features may further improve the predicted quality. RESULTS: In this article, we provide a novel multi-label classifier, called iATC-NRAKEL, to predict drug ATC classes in the first level. To obtain more informative drug features, we employed the drug association information in STITCH and KEGG, which was organized by seven drug networks. The powerful network embedding algorithm, Mashup, was adopted to extract informative drug features. The obtained features were fed into the RAndom k-labELsets (RAKEL) algorithm with support vector machine as the basic classification algorithm to construct the classifier. The 10-fold cross-validation of the benchmark dataset with 3883 drugs showed that the accuracy and absolute true were 76.56 and 74.51%, respectively. The comparison results indicated that iATC-NRAKEL was much superior to all previous reported classifiers. Finally, the contribution of each network was analyzed. AVAILABILITY AND IMPLEMENTATION: The codes of iATC-NRAKEL are available at https://github.com/zhou256/iATC-NRAKEL.

Synergistic bactericidal effects of pairs of photosensitizer molecules activated by ultraviolet A light against bacteria in plasma.

BACKGROUND: The current approach to reducing bacterial contamination in blood transfusion products is through detection or pathogen reduction methods, some of which utilize ultraviolet (UV) light photosensitizers. A small number of photosensitizers are being used as single agents in combination with UV light, but their efficacy can be limited against some pathogens. Benzophenone (BP) and vitamins B1, B6, and K3 have been identified as effective UVA photosensitizers for inactivation of bacteria. We evaluated whether combining pairs of photosensitizers in this group would have synergistic bactericidal effects on Gram-negative and Gram-positive bacteria. STUDY DESIGN AND METHODS: Bacteria species of Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Klebsiella pneumoniae were mixed with 0 to 100 mM concentrations of photosensitizers and exposed to UVA irradiation at 18 J/cm2 to assess their bactericidal effects. RESULTS: Single photosensitizers irradiated with UVA produced a range of bactericidal activity. When combined in pairs, all demonstrated some synergistic bactericidal effects with up to 4-log reduction above the sum of activities of individual molecules in the pair against bacteria in plasma. Photosensitizer pairs with BP had the highest synergism across all bacteria. With vitamin K3 in the pair, synergism was evident for Gram-positive but not for Gram-negative bacteria. Vitamin B1 and vitamin B6 had the least synergism. These results indicate that a combination approach with multiple photosensitizers may extend effectiveness of pathogen reduction in plasma. CONCLUSIONS: Combining photosensitizers in pathogen reduction methods could improve bactericidal efficacy and lead to use of lower concentrations of photosensitizers to reduce toxicities and unwanted side effects.

Cardiac Myosin Promotes Thrombin Generation and Coagulation In Vitro and In Vivo.

OBJECTIVE: Cardiac myosin (CM) is structurally similar to skeletal muscle myosin, which has procoagulant activity. Here, we evaluated CM's ex vivo, in vivo, and in vitro activities related to hemostasis and thrombosis. Approach and Results: Perfusion of fresh human blood over CM-coated surfaces caused thrombus formation and fibrin deposition. Addition of CM to blood passing over collagen-coated surfaces enhanced fibrin formation. In a murine ischemia/reperfusion injury model, exogenous CM, when administered intravenously, augmented myocardial infarction and troponin I release. In hemophilia A mice, intravenously administered CM reduced tail-cut-initiated bleeding. These data provide proof of concept for CM's in vivo procoagulant properties. In vitro studies clarified some mechanisms for CM's procoagulant properties. Thrombin generation assays showed that CM, like skeletal muscle myosin, enhanced thrombin generation in human platelet-rich and platelet-poor plasmas and also in mixtures of purified factors Xa, Va, and prothrombin. Binding studies showed that CM, like skeletal muscle myosin, directly binds factor Xa, supporting the concept that the CM surface is a site for prothrombinase assembly. In tPA (tissue-type plasminogen activator)-induced plasma clot lysis assays, CM was antifibrinolytic due to robust CM-dependent thrombin generation that enhanced activation of TAFI (thrombin activatable fibrinolysis inhibitor). CONCLUSIONS: CM in vitro is procoagulant and prothrombotic. CM in vivo can augment myocardial damage and can be prohemostatic in the presence of bleeding. CM's procoagulant and antifibrinolytic activities likely involve, at least in part, its ability to bind factor Xa and enhance thrombin generation. Future work is needed to clarify CM's pathophysiology and its mechanistic influences on hemostasis or thrombosis.

Molecular interaction site on procoagulant myosin for factor Xa-dependent prothrombin activation.

Skeletal muscle myosin has potent procoagulant activity that is based on its ability to enhance thrombin generation due to binding coagulation factors Xa and Va and accelerating prothrombin activation. A well-studied myosin inhibitor that binds to myosin's neck region inhibits myosin-dependent prothrombin activation. Hence, to identify a potential binding site(s) on skeletal muscle myosin for factor Xa, 19 peptides (25-40 residues) representing the neck region, which consists of a regulatory light chain, an essential light chain, and a heavy chain (HC), were screened for inhibition of myosin-supported prothrombin activation. Peptide HC796-835 comprising residues 796-835 of the heavy chain strongly inhibited myosin-enhanced prothrombin activation by factors Xa and Va (50% inhibition at 1.2 µm), but it did not inhibit phospholipid vesicle-enhanced prothrombin activation. Peptide inhibition studies also implicated several myosin light chain sequences located near HC796-835 as potential procoagulant sites. A peptide comprising HC796-835's C-terminal half, but not a peptide comprising its N-terminal half, inhibited myosin-enhanced prothrombin activation (50% inhibition at 1.2 µm). This inhibitory peptide (HC816-837) did not inhibit phospholipid-enhanced prothrombin activation, indicating its specificity for inhibition of myosin-dependent procoagulant mechanisms. Binding studies showed that purified factor Xa was bound to immobilized peptides HC796-835 and HC816-837 with apparent Kd values of 0.78 and 1.3 µm, respectively. In summary, these studies imply that HC residues 816-835 in the neck region of the skeletal muscle myosin directly bind factor Xa and, with contributions from light chain residues in this neck region, contribute to provision of myosin's procoagulant surface.

New insights into the release mechanism of Cd2+ from CdTe quantum dots within single cells in situ.

Cadmium-quantum dots (Cd-QDs) possess unique properties as optoelectronic devices for sensitive detection in food and biomedicine fields. However, the toxic effects of Cd-QDs to single cells is still controversial, due to the release mechanism of QDs to Cd2+in situ and the cytotoxic effects of QDs and Cd2+ respectively are still unclear. In this paper, the release rule of Cd2+ from CdTe QDs within single cells was investigated in situ by using flow cytometry method and the dose-response relationships were explored. Besides, an all-inclusive microscopy system was optimized for live cell imaging to observe the real-time entry process of CdTe QDs into cells. We found that intracellular CdTe QDs and Cd2+ contents were increased based on the dosage and exposing time. A dissociated saturation of Cd2+ from CdTe QDs was exist within cells. CdTe QDs induced more serious cytotoxicity on kidney cells than hepatocytes. The toxicity of oxidative stress, cell apoptosis effects induced by CdTe QDs and Cd2+ are also in consistent with this result. This research develops analytical method to quantify the uptake and release of Cd-QDs to primary cells in situ and can provide technical support in studying the cytotoxicity portion contributed by nanoparticles (NPs) and metal ions.