A compact microfluidic platform for rapid multiplex detection of respiratory viruses via centrifugal polar-absorbance spectroscopy.

Nucleic acid detection technology has become a crucial tool in cutting-edge research within the life sciences and clinical diagnosis domains. Its significance is particularly highlighted during the respiratory virus pandemic, where nucleic acid testing plays a pivotal role in accurately detecting the virus. Isothermal amplification technologies have been developed and offer advantages such as rapidity, mild reaction conditions and excellent stability. Among these methods, recombinase polymerase amplification (RPA) has gained significant attention due to its simple primer design and resistance to multiple reaction inhibitors. However, the detection of RPA amplicons hinders the widespread adoption of this technology, leading to a research focus on cost-effective and convenient detection methods for RPA nucleic acid testing. In this study, we propose a novel computational absorption spectrum approach that utilizes the polar GelRed dye to efficiently detect RPA amplicons. By exploiting the asymmetry of GelRed molecules upon binding with DNA, polar electric dipoles are formed, leading to precipitate formation through centrifugal vibration and electrostatic interaction. The quantification of amplicon content is achieved by measuring the residual GelRed concentration in the supernatant. Our proposed portable and integrated microfluidic device successfully detected five respiratory virus genes simultaneously. The optimized linear detection was achieved and the sensitivity for all the targets reached 100 copies/µL. The total experiment could be finished in 27 min. The clinical experiments demonstrated the practicality and accuracy. This cost-effective and convenient detection scheme presents a promising biosensor for rapid virus detection, contributing to the advancement of RPA technology.

Interaction between BDNF Val66Met polymorphism and mismatch negativity for working memory capacity in schizophrenia.

Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

Self-crosslinking hyaluronic acid-based hydrogel with promoting vascularization and ROS scavenging for wound healing.

Skin wound dressings are commonly utilized for the treatment of skin injuries, as they effectively facilitate wound healing and possess anti-inflammatory and antibacterial properties. However, conventional dressings fail to inhibit ROS production and promote vascularization, leading to delayed wound healing. Here, we developed injectable self-crosslinking hydrogels through thiolated hyaluronic acid (HASH/rhCOLIII) with enhancing the ROS inhibitory capacity while preserving the cell adhesion ability of hyaluronic acid. Additionally, recombinant humanized collagen type III (rhCOLIII) is incorporated via electrostatic adsorption to further enhance mechanical strength and angiogenesis properties of the hydrogel. The HASH/rhCOLIII demonstrated excellent biocompatibility, remarkable ROS scavenging ability, as well as hemostatic and angiogenic properties. Cell experiment results show that HASH/rhCOLIII has excellent biocompatibility and can significantly promote angiogenesis. Animal experiments results showed that HASH/rhCOLIII exhibits anti-inflammatory effects, significantly accelerating wound healing in a full-thickness skin defect model. These findings highlight that HASH/rhCOLIII hydrogel holds great promise as an advanced dressing for effective wound healing.

Small cell lung carcinoma with KIF5B-RET fusion partially responded to the 4th-line therapy with anlotinib: A case report.

BACKGROUND: Small cell lung cancer (SCLC) exhibits a pronounced tendency for metastasis and relapse, and the acquisition of resistance to chemotherapy and radiotherapy, leading to complexity in treatment outcomes. It is crucial to tackle these challenges by advancing targeted therapeutic approaches in ongoing research endeavors. Variant RET fusions have been reported in several solid tumors, but are rarely reported in SCLC. CASE SUMMARY: We present the first case of a KIF5B-RET fusion in a 65-year-old male patient with SCLC. To date, the patient has received the 4th line chemotherapy with anlotinib for one year and has shown a sustained favorable partial response. According to the results of next generation sequencing, this SCLC patient harbors the KIF5B-RET fusion, suggesting that RET fusion could serve as a promising molecular target for SCLC treatment. Next-generation sequencing (NGS) plays a critical role in comprehensively assessing the genotype and phenotype of cancer. CONCLUSION: NGS can provide SCLC patients with personalized and targeted therapy options, thereby improving their likelihood of survival.

Variational quantum algorithm for node embedding.

Quantum machine learning has made remarkable progress in many important tasks. However, the gate complexity of the initial state preparation is seldom considered in lots of quantum machine learning algorithms, making them non-end-to-end. Herein, we propose a quantum algorithm for the node embedding problem that maps a node graph's topological structure to embedding vectors. The resulting quantum embedding state can be used as an input for other quantum machine learning algorithms. With O ( log ( N ) ) qubits to store the information of N nodes, our algorithm will not lose quantum advantage for the subsequent quantum information processing. Moreover, owing to the use of a parameterized quantum circuit with O ( poly ( log ( N ) ) ) depth, the resulting state can serve as an efficient quantum database. In addition, we explored the measurement complexity of the quantum node embedding algorithm, which is the main issue in training parameters, and extended the algorithm to capture high-order neighborhood information between nodes. Finally, we experimentally demonstrated our algorithm on an nuclear magnetic resonance quantum processor to solve a graph model.

Ultrasensitive detection platform for Staphylococcus aureus based on DNAzyme tandem blocking CRISPR/Cas12a system.

Detection methods based on CRISPR/Cas12a have been widely developed in the application of pathogenic microorganisms to guarantee food safety and public health. For sensitive detection, the CRISPR-based strategies are often in tandem with amplification methods. However, that may increase the detection time and the process may introduce nucleic acid contamination resulting in non-specific amplification. Herein, we established a sensitive S. aureus detection strategy based on the CRISPR/Cas12a system combined with DNAzyme. The activity of Cas12a is blocked by extending the spacer of crRNA (bcrRNA) and can be reactivated by Mn2+. NH2-modified S. aureus-specific aptamer was loaded on the surface of Fe3O4 MNPs (apt-Fe3O4 MNPs) and MnO2 NPs (apt-MnO2 NPs) by EDC/NHS chemistry. The S. aureus was captured to form apt-Fe3O4 MNPs/S. aureus/apt-MnO2 NPs complex and then MnO2 NPs were etched to release Mn2+ to activate DNAzyme. The active DNAzyme can cleave the hairpin structure in bcrRNA to recover the activity of the CRISPR/Cas system. By initiating the whole detection process by generating Mn2+ through nanoparticle etching, we established a rapid detection assay without nucleic acid extraction and amplification process. The proposed strategy has been applied in the ultrasensitive quantitative detection of S. aureus and has shown good performance with an LOD of 5 CFU/mL in 29 min. Besides, the proposed method can potentially be applied to other targets by simply changing the recognition element and has the prospect of developing a universal detection strategy.

Machine Learning Assisted MALDI Mass Spectrometry for Rapid Antimicrobial Resistance Prediction in Clinicals.

Antimicrobial susceptibility testing (AST) plays a critical role in assessing the resistance of individual microbial isolates and determining appropriate antimicrobial therapeutics in a timely manner. However, conventional AST normally takes up to 72 h for obtaining the results. In healthcare facilities, the global distribution of vancomycin-resistant Enterococcus fecium (VRE) infections underscores the importance of rapidly determining VRE isolates. Here, we developed an integrated antimicrobial resistance (AMR) screening strategy by combining matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) with machine learning to rapidly predict VRE from clinical samples. Over 400 VRE and vancomycin-susceptible E. faecium (VSE) isolates were analyzed using MALDI-MS at different culture times, and a comprehensive dataset comprising 2388 mass spectra was generated. Algorithms including the support vector machine (SVM), SVM with L1-norm, logistic regression, and multilayer perceptron (MLP) were utilized to train the classification model. Validation on a panel of clinical samples (external patients) resulted in a prediction accuracy of 78.07%, 80.26%, 78.95%, and 80.54% for each algorithm, respectively, all with an AUROC above 0.80. Furthermore, a total of 33 mass regions were recognized as influential features and elucidated, contributing to the differences between VRE and VSE through the Shapley value and accuracy, while tandem mass spectrometry was employed to identify the specific peaks among them. Certain ribosomal proteins, such as A0A133N352 and R2Q455, were tentatively identified. Overall, the integration of machine learning with MALDI-MS has enabled the rapid determination of bacterial antibiotic resistance, greatly expediting the usage of appropriate antibiotics.

Assessing the accuracy of reporting of hypertension on death certificates in Australia.

BACKGROUND: There is insufficient evidence of how accurately hypertension is reported on death certificates, which are the primary evidence of causes of death. This study assesses the accuracy of reporting of hypertension on death certificates of decedents in Australia who previously had their blood pressure measured. METHODS: Blood pressure data from the 2014-15 and 2017-18 National Health Surveys were linked to death registration data from July 2015-December 2021 (average 3.3 years from survey to death). The percentage of decedents with hypertension reported on the death certificate was calculated according to blood pressure level and previous diagnosis of hypertension. RESULTS: Hypertension was reported on the death certificate of 20.2% (95% confidence interval 12.1-28.3%) of decedents who had very high to severe blood pressure (160/100 mmHg and above), 14.5% (10.3-18.8%) who had high blood pressure (140/90 mmHg to less than 160/100 mmHg), 14.1% (10.8%-17.4%) who had normal to high blood pressure (less than 140/90 mmHg) and who took hypertension medication, and 17.8% (13.6-22.0%) who had been diagnosed with hypertension. Where the decedent had very high to severe blood pressure, hypertension was reported for 27.9% (14.1-41.8%) of deaths if they had been diagnosed with hypertension and 21.7% (9.6-33.7%) where another cardiovascular disease was reported on the death certificate. CONCLUSIONS: Hypertension mortality in Australia is only reported for a minority of deaths of people with high or very high to severe blood pressure; this is also found for those with a prior diagnosis of hypertension.

The Velvet transcription factor PnVeA regulates necrotrophic effectors and secondary metabolism in the wheat pathogen Parastagonospora nodorum.

The fungus Parastagonospora nodorum causes septoria nodorum blotch on wheat. The role of the fungal Velvet-family transcription factor VeA in P. nodorum development and virulence was investigated here. Deletion of the P. nodorum VeA ortholog, PnVeA, resulted in growth abnormalities including pigmentation, abolished asexual sporulation and highly reduced virulence on wheat. Comparative RNA-Seq and RT-PCR analyses revealed that the deletion of PnVeA also decoupled the expression of major necrotrophic effector genes. In addition, the deletion of PnVeA resulted in an up-regulation of four predicted secondary metabolite (SM) gene clusters. Using liquid-chromatography mass-spectrometry, it was observed that one of the SM gene clusters led to an accumulation of the mycotoxin alternariol. PnVeA is essential for asexual sporulation, full virulence, secondary metabolism and necrotrophic effector regulation.

[Retracted] Effects of RUNX3 mediated Notch signaling pathway on biological characteristics of colorectal cancer cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell apoptotic data shown in Fig. 5A on p. 2065, and the Transwell migration and invasion assay data shown in Fig. 6A and C on p. 2066 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to International Journal of Oncology, or were submitted for publication at around the same time. Given that the abovementioned data had already apparently been published previously, the Editor of International Journal of Oncology has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 50: 2059­2068, 2017; DOI: 10.3892/ijo.2017.3988].

Metabolic Dysfunction-associated Steatotic Liver Disease is Becoming the Leading Driver of the Burden of Cirrhosis in China: Results From the Global Burden of Disease Study 2019.

OBJECTIVE: Cirrhosis and other chronic liver diseases (generally referred to as cirrhosis in this article) are major causes of morbidity and mortality in China. The disease pattern of cirrhosis caused by different etiologies has been changing due to economic development and changes in lifestyle. METHODS: Prevalence, incidence, disability-adjusted life-years, and mortality data were retrieved from the Global Burden of Disease study, 2019. Estimated annual percentage change was used to quantify the trends in the age-standardized prevalence rate and prevalence number of cirrhosis from 1990 to 2019. We presented the results for five causes of cirrhosis, and for different age and sex groups. RESULTS: Nationwide, we found that the prevalence number of liver cirrhosis increased steadily (from 3025.3×105 to 4279.8×105) from 1990 to 2019. Notably, the age-standardized prevalence rate of cirrhosis caused by metabolic dysfunction-associated steatotic liver disease (MASLD) increased throughout the study period, and MASLD has exceeded the hepatitis B virus and become the leading cause of liver cirrhosis since 1992. The highest prevalence number of MASLD occurred in the young population aged between 15 to 49 years. CONCLUSION: The prevalence of liver cirrhosis caused by hepatitis B virus decreased, whereas the prevalence of liver cirrhosis caused by MASLD increased. MASLD has become the leading cause of liver cirrhosis in China. The prevalence of liver cirrhosis increased most significantly in the young age group compared with the other age group. Preventive strategies targeting MASLD would be necessary to reduce the disease burden of cirrhosis in China, especially in the young aged generation.

Moral courage level of nurses: a systematic review and meta-analysis.

BACKGROUND: Moral distress occurs in daily nursing work and plagues nurses. Improving the level of moral courage is one of the main strategies to reduce moral distress, and low levels of moral courage may lead to nurse burnout, increased turnover, and reduced quality of care. METHODS: Nine electronic databases in Chinese and English were searched for the level of moral courage among nurses, including PubMed, Web of Science, EMBASE, CINAHL, CNKI, Wan fang, Wei pu, CBM and Cochrane Library, for the period from the date of database creation to April 5, 2023. The Agency for Healthcare Research and Quality (AHRQ) was used to assess the methodological quality of the included studies, followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Meta-analysis and Systematic Reviews of Observational Studies guidelines, and data from the included studies were meta-analyzed in STATA version 15 using a fixed-effects model. RESULTS: Seventeen cross-sectional studies of moderate or high quality met the eligibility criteria and involved 7718 nurses, and the Nurses' Moral Courage Scale (NMCS) was used to measure the self-assessed moral courage level of nurses. Eleven of these studies reported total scores for nurses' moral courage, and the meta-analysis results showed a pooled mean score of 78.94 (95% CI: 72.17, 85.72); Fourteen studies reported mean entry scores for nurses' moral courage, and the meta-analysis results showed a pooled mean score of 3.93 (95% CI: 3.64, 4.23). CONCLUSION: The results of the meta-analysis showed that nurses' moral courage levels were in the medium to high range, among the nurses who seemed to be male, non-nursing managers, high school education, had not experienced ethical issues, and considering resignation had lower levels of moral courage. The results of the meta-analysis may provide some reference for nursing managers and even hospital administrators to develop strategies to optimize nursing quality.

Comprehensive macro and micro views on immune cells in ischemic heart disease.

Ischemic heart disease (IHD) is a prevalent cardiovascular condition that remains the primary cause of death due to its adverse ventricular remodelling and pathological changes in end-stage heart failure. As a complex pathologic condition, it involves intricate regulatory processes at the cellular and molecular levels. The immune system and cardiovascular system are closely interconnected, with immune cells playing a crucial role in maintaining cardiac health and influencing disease progression. Consequently, alterations in the cardiac microenvironment are influenced and controlled by various immune cells, such as macrophages, neutrophils, dendritic cells, eosinophils, and T-lymphocytes, along with the cytokines they produce. Furthermore, studies have revealed that Gata6+ pericardial cavity macrophages play a key role in regulating immune cell migration and subsequent myocardial tissue repair post IHD onset. This review outlines the role of immune cells in orchestrating inflammatory responses and facilitating myocardial repair following IHD, considering both macro and micro views. It also discusses innovative immune cell-based therapeutic strategies, offering new insights for further research on the pathophysiology of ischemic heart disease and immune cell-targeted therapy for IHD.

Intensity and associated factors of home health care service needs among elderly patients with chronic diseases in the community: A cross-sectional survey.

AIM AND OBJECTIVES: This study aimed to investigate the intensity of needs for home health care services (HHCs) among elderly patients with chronic diseases and to identify the associated factors. DESIGN: A cross-sectional survey was conducted in Wuhou District, Chengdu, Sichuan Province, China, from April to November 2021. METHODS: Convenient sampling was used to screen elderly patients with chronic diseases managed by Yulin Community Health Service Center. The questionnaires included general information and the Chinese version of the Community Healthy Intensity Rating Scale were completed according to patients' conditions. The data were analyzed using descriptive statistics and binary logistic regression. RESULTS: A total of 371 patients (10.40%) completed the survey. The mean age of the elderly patients was 84.04 years (SD = 7.07); these patients suffered from 1 to 7 kinds of chronic diseases, and the most common were hypertension (78.98%) and diabetes (40.97%). The need intensity of patients for HHCs was moderate (41.51%) or severe (58.49%). For each additional chronic disease that patients suffered from, the need intensity increases by 1.289 times (OR = 1.289; 95% CI: 1.055-1.575, p = .013); in additional, those aged more than 90 years, with a personal monthly income less than 2500 yuan ($387.00), with a poor health current status, and with only basic medical insurance presented greater need intensity (p < .05). CONCLUSION: Our data analysis revealed that economic status, insurance condition, poor health status, and multiple comorbidities may be the most common factors associated with the need intensity for HHCs. These characteristics may help medical staff to identify and help those with urgent health problems.

Transcutaneous oxygen tension-guided hyperbaric oxygen therapy for preventing skin necrosis after hyaluronic acid filler injections.

Introduction: Hyaluronic acid (HA) fillers, popular for facial cosmetic enhancements, pose risks of vascular complications like skin necrosis due to arterial blockage, necessitating effective treatments such as hyperbaric oxygen therapy (HBOT). Methodology: This study presents a series of cases where measurements of transcutaneous oxygen pressure (TcPO2) informed the application of HBOT for skin necrosis induced by HA. Clinical presentation and outcomes: In cases 1 and 3, following the injection of HA, potential skin necrosis was observed. In addition to standard treatment, TcPO2 revealed values below 40 mmHg, indicating tissue hypoxia. Treatment with HBOT increased TcPO2 levels to above 200 mmHg, suggesting that HBOT could correct the hypoxia. Monitoring TcPO2 levels also aided in determining the optimal time to discontinue HBOT. In cases 2 and 4, patients received standard treatment, resulting in TcPO2 levels above 40 mmHg, indicating adequate tissue oxygenation, and no additional HBOT was administered. All four patients mentioned above showed good clinical recovery. Conclusion: This study investigates the application of TcPO2 measurement technology in aiding decisions on whether to utilize HBOT in the treatment of complications arising from HA fillers, as well as in optimizing HBOT protocols.

Effect of transcranial direct current stimulation with concurrent cognitive performance targeting posterior parietal cortex vs prefrontal cortex on working memory in schizophrenia: a randomized clinical trial.

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.