bluuebunny/crossref_metadata_2025 huggingface dataset:
CircGRB10 Mitigates Ischemic Neuronal Injuries through Ferroptosis Regulation via miR-6838-5p/FBXW7 Axis
Authors: Chen Wanghao , Yu Qiang , Yang Xiaoshen , Zhang Wenchuan
Published: May 2024

Circular RNAs (circRNAs) exhibit widespread expression within the brain and are pivotal in the development of numerous central nervous system disorders, particularly in neuronal damage associated with ischemic stroke. Our research focuses on mmu_circ_0009119 (circGRB10) and its pivotal role in this process. Through studies on healthy controls and ischemic stroke patients, along with in vitro simulations using the oxygen and glucose deprivation/reoxygenation (OGD/R) model in HT22 neuronal cells, we revealed a significant upregulation of circGRB10 in a mouse model of ischemic stroke. Deficiency in circGRB10 restored cell viability in OGD/R-induced HT22 cells by upregulating FBXW7 through sequestering miR-6838-5p. Inhibition of miR-6838-3p weakened the impact of circGRB10 silencing on cell survival and Ferroptosis in OGD/R-induced HT22 cells. Additionally, the upregulation of FBXW7 counteracted the effect of miR-6838-5p upregulation on OGD/R-induced HT22 cells. On another note, circGRB10 suppressed cell survival and accelerated Ferroptosis in OGD/R-induced HT22 cells by sequestering miR-6838-5p to upregulate the FBXW7 axis. This study elucidates the mechanism by which circGRB10, through the circGRB10/miR-6838-5p/FBXW7 axis, regulates neuronal survival after ischemic stroke, providing crucial insights into its potential as a therapeutic target for ischemic stroke.
Evaluation of the efficacy of rat renal ischemia-reperfusion injury after itaconic acid and its isomers treatment by contrast-enhanced ultrasound(CEUS)
Authors: Tang Bin , luo zhijian , Zhang Rong , Zhang Dongmei , Li Mingxing , Dai Yan
Published: May 2024

Itaconic acid and its isomers citraconic acid and mesaconic acid are a recently discovered class of metabolites with anti-inflammatory and antioxidant effects. This study will investigate its role in ischemia-reperfusion-induced acute kidney injury, and use contrast-enhanced ultrasound to evaluate kidney function, in order to provide a new diagnostic method and treatment strategy for renal acute kidney injury. In this study, a rat model of renal ischemia-reperfusion was established, and itaconic acid, citraconic acid and mesaconic acid were given as preoperative intervention. After the operation, the rat kidneys were examined by contrast-enhanced ultrasound, biochemical analysis and pathological staining. The results showed that the intervention of itaconic acid, citraconic acid and mesaconic acid could effectively reduce renal ischemia-reperfusion injury through anti-inflammatory and antioxidant effects,and inhibiting cell pyroptosis. These findings suggest that itaconic acid, citraconic acid, and mesaconic acid may be effective strategies for the treatment of renal ischemia-reperfusion through Inflammation-related pyroptosis pathway.
Effective removal of toxic Cd(II) ions from aqueous solution using mixed macroalgal adsorbent: Kinetics and ANN modeling studies
Authors: Thamarai P , Deivayanai V C , Karishma S , Anbalagan Saravanan , Yaashikaa P. R. , Vickram A.S.
Published: May 2024

The research focuses on examining the biosorption capability of raw mixed seaweed biosorbent (RMSB) for the removal of the hazardous metal cadmium (II) under controlled environmental conditions. Using techniques such as elemental dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR), biosorbent was characterized. The impacts of adsorbent dosage, contact time, initial Cd concentration, pH, and temperature have been assessed for the removal of Cd (II) and its adsorption. Optimum levels - pH, biosorbent mass, contact duration, and temperature were 5, 2 g/L, 50 minutes, and 303 K, respectively. The optimum intake of metals Cd (II) has been evaluated with isotherm modeling. Single-layer sorption was confirmed by the Freundlich isotherm, which proved to be an excellent fit. Maximum potential adsorption of Cd (II) was 146.2 mg/g. The biosorption kinetics of Cd (II) onto RMSB exhibit pseudo-first-order behaviour. The feasibility of the sorption process was established, and the thermodynamic parameters were determined. The Cd (II) sorption onto RMSB biomass has been estimated through the use of artificial neural networks (ANNs). With the high cross-correlation coefficient (R) value, the ANN models predicted the Cd (II) adsorption onto RMSB with remarkable accuracy. The outcomes showed that Cd (II) may be effectively removed from the aqueous solution using RMSB.
Enhancing Teacher Status in Kazakhstan: The Role of School Leaders and Legislative Measures
Authors: Sarmurzin Yerbol
Published: May 2024

This article presents research on the role of school leaders in improving teachers’ status in Kazakhstan. The research uses a mixed-methods approach, integrating data from questionnaires and semi-structured interviews. The findings demonstrate a positive attitude towards legislative measures. Nevertheless, there is a gap between policy and reality, since school leaders often violate legal obligations. The study highlights the vital role of school leaders in offering support and chances for professional growth, which greatly impacts teachers' views of their standing and level of work satisfaction. In addition, the research reveals that the built environment of schools and their academic rankings have a role in determining the social status of teachers. The results underscore the significance of successful policy implementation, increased support from school administrators, and a concentration on teacher welfare to raise their professional status. The findings of this study are of great importance for policymakers, school administrators, and educators.
A Novel Approach to Classifying Chemotherapeutic Agents Based on Their Impact on Canonical Pathways: Implications for Overcoming Multidrug Resistance in Breast Cancer
Authors: Batha Lin , Zhra Mahmoud , Galal Mariam Ahmed , Holail Jasmine , Aldossari Fai , Aziz Mohammad Azhar , Alzayer Maha , Fakhoury Rajaa , Aljada Ahmad
Published: May 2024

Introduction: Breast cancer faces a significant challenge in the form of multidrug resistance (MDR), which requires the development of innovative therapeutic approaches. This study investigates the molecular mechanisms underlying MDR in MCF7 breast cancer cells to identify common signaling pathways that contribute to resistance. Additionally, this research aims to propose a novel classification system for chemotherapeutic agents based on their influence on these pathways.
Methodology: To create drug-resistant MCF7 sublines, MCF7 cells were subjected to chemotherapeutic drugs for 12 months, with concentrations gradually increasing over time. The transcriptome of these sublines was then analyzed using next-generation RNA sequencing through Ion Torrent technology. Differentially expressed genes (DEGs) and their associated canonical pathways, molecular functions, and upstream regulators were identified using Ingenuity Pathway Analysis (IPA).
Results: Unique mRNA expression patterns were associated with chemoresistance, indicating notable up- and downregulation patterns of DEGs in MCF7 chemoresistant subline cells. The use of IPA allowed for the categorization of chemotherapeutic drugs into three groups based on their effects on canonical pathways: Group I (Arabinosylcytosine, Methotrexate), Group II (Paclitaxel, Cyclophosphamide, Nocodazole), and Group III (5-Fluorouracil, Etoposide, Doxorubicin, Cisplatin).
Conclusion: A new approach to enhance the effectiveness of breast cancer chemotherapy is proposed. This approach involves categorizing chemotherapeutic agents based on their impact on canonical pathways. The innovative classification system has the potential to guide the development of combination therapies, predict drug resistance mechanisms, and ultimately improve patient outcomes. However, it is essential to conduct extensive research and validate these findings in other breast cancer cell lines and clinical settings.
Relationship between physical activity, sleep quality, and frailty in middle-aged and older adults: a cross-sectional study Running title: The correlation between physical activity, sleep quality, and frailty
Authors: SUI Linpeng , ZHANG Donglin , WANG Wenhua , LI Dan , LIU Yue , XUE Mei , HAO Jianfeng , WANG Minjuan , ZHANG Lei
Published: May 2024

Background: Frailty is linked to numerous negative health consequences, with past research indicating that physical activity (PA) and sleep quality play a role in influencing frailty among older adults. As societal norms evolve, middle-aged adults are faced with time constraints that may result in differences in PA and sleep compared to older adults. Despite this, there is a limited amount of research focusing on middle-aged and older adults. This study seeks to examine the prevalence of frailty among middle-aged and older adults in the region, as well as investigate the connection between sleep quality, PA, and frailty.
Methods: This cross-sectional study involved 1,265 middle-aged and elderly permanent residents from a region in Shaanxi Province, China. Participants were selected randomly for a physical examination and questionnaire survey. The questionnaires covered sociodemographic information, the Frailty Scale, the Pittsburgh Sleep Quality Index (PSQI) Scale, and the International Physical Activity Questionnaire (IPAQ). Statistical description and correlation analysis between variables were conducted using SPSS software.
Results: A total of 1042 study participants were ultimately included in the analysis, with 74 classified as frailty and 444 as non-frailty. Adjusting for relevant covariates revealed that middle-aged and older adults engaging in light PA were more likely to be frailty compared to those with high PAL during non-frailty (CI 0.149-0.682; P < 0.01) and pre-frailty stages (CI 0.098-0.425; P < 0.001). Conversely, individuals without sleep disorders were less likely to be frailty (CI 1.241-3.720; P < 0.01). Occupational MET values were highest during the pre-frailty period in the presence of substantial PA (P < 0.001). Sleep quality not only directly predicted frailty but also acted as a mediator in influencing the role of age on frailty, with a mediating effect of 12.43%.
Conclusion: Both PA and sleep quality play a role in frailty. The impact of PA on frailty is influenced by the nature of the individual's occupation. Sleep disorders can heighten the risk of frailty, with sleep quality acting as a mediator in the relationship between age and frailty.
Interferon-γ blockade in CD19 CART cell therapy-induced secondary macrophage activation syndrome/hemophagocytic lymphohistiocytosis
Authors: Shen Haihao , Zhang Mengyue , Pan Ying , Peng Peng , Wang Zhitao , Yao Cunying , Zhou Li
Published: May 2024

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a highly effective therapy for hematological malignancies. Macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH) is one of the most serious adverse events of CART-cell therapy. We report a case of CD19+ B ALL patient who was treated with autologous CD19-CART cells and developed a life-threatening secondary MAS/HLH. Her MAS/HLH was successfully salvaged treated by blocking Interferon-γ using emapalumab. Our case showed that emapalumab was a good option for the treatment of patients in CART cell therapy-induced secondary MAS/HLH without deleterious effect on the efficacy of CART cells in short term. It gave clinicians new inspiration.
Rosuvastatin calcium and pravastatin sodium regulate the antioxidant system in zebrafish liver by inhibiting the PI3K/Nrf2/ARE signaling pathway
Authors: WANG XIANRUI , MU QUANLING , LI XIAOLONG , SHI JIAYE , LI RUMENG , ZHAO YE , DING CUNBAO
Published: May 2024

Rosuvastatin calcium (ROV) and pravastatin sodium (PRA) are commonly used drugs for the treatment and prevention of cardiovascular diseases, but as a result, they have been reported to be present worldwide in aquatic environments. However, little is known about the effects of ROV or PRA on fish antioxidant systems and the underlying molecular mechanisms. In this study, zebrafish were exposed to ROV or PRA for 48 h, to explore their effects on the antioxidant response system in zebrafish liver and its possible molecular mechanism. The results showed that the contents of reactive oxygen species (ROS)and glutathione (GSH) increased significantly after ROV exposure, while the activities of catalase (CAT)and superoxide dismutase (SOD) were significantly inhibited. Glutathione peroxidase (GPx) and glutathione peroxidase (GST) were activated after exposure to 5 mg/L ROV, and malondialdehyde (MDA) content increased after 0.5 mg/L ROV exposure. Phosphoinositide 3-kinase (PI3K) and CAT were activated at the mRNA level only after 5 mg/L ROV exposure, while nuclear factor erythroid 2-like 2 (Nrf2) and SOD were inhibited at the protein level. After adding PI3K activator 740Y-P, the protein inhibition of Nrf2 and SOD was reversed. After PRA exposure, the contents of ROS, GSH and MDA were activated, the activities of CAT and SOD were significantly inhibited, and GST was activated only after 10 mg/L PRA exposure. At the mRNA level, 10mg/L PRA activated PI3K, CAT and GPx, while Nrf2 and SOD were inhibited at the protein level. Similarly, after the addition of the PI3K activator 740Y-P, inhibition of both Nrf2 and SOD protein was abolished. Further molecular docking simulations showed that ROV and PRA could spontaneously dock with PI3K and form stable interactions through hydrogen bonds. In summary, both ROV and PRA induce significant oxidative stress in zebrafish liver, and both ROV and PRA act as PI3K inhibitors to block the activation of the nuclear factor erythroid 2-like 2/antioxidant response element (Nrf2/ARE) signaling pathway, thereby reducing the antioxidant capacity in zebrafish liver.
Prostaglandins as Vasodilatory Agent Therapy for Pulmonary Hypertension in Postnatal Period in Patients with Congenital Diaphragmatic Hernia: A Systematic Review and Meta- Analysis
Authors: Cabral Tayenne , melchior Camila , Clavi Izabela , Lisboa Priscila , Magalhaes Debora
Published: May 2024

Purpose
Congenital diaphragmatic hernia (CDH) represents a deviation in lung development and a life-threatening condition with high mortality rate. [1–5] The study aimed to perform a meta-analysis on the efficacy and safety of prostaglandins as vasodilatory agent therapy for Pulmonary Hypertension (PH) in postnatal period in patients with Congenital Diaphragmatic Hernia.
Methods
A systematic search of PubMed, EMBASE, and Cochrane was conducted to identify randomized controlled trials (RCT) and cohorts analyzing the use of PGE1 and PGI versus placebo in CDH patients with PH born after 37 weeks of gestation. The primary outcomes of interest were mortality and ECMO utilization. Statistical analysis followed the Cochrane Collaboration guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. Heterogeneity was assessed by using Cochrane's Risk of Bias 1 (ROBINS-I), Cochran Q test, and I2 statistics.
Results
The meta-analysis, comprising four cohorts totaling 6,873 patients, revealed that prostaglandins (PG) did not significantly decrease mortality rates as anticipated (RR 1.44; 95% CI 0.89–2.32; p = 0.134; I2 = 64%). However, the confidence interval and p-value indicated a lack of statistical significance.
Conclusion
This meta-analysis has its limitations; we do not establish conclusively the efficacy of PGI and PGE in reducing mortality in CDH patients. However, it may have indicated an association between the use of PGE1 and a reduction in the duration of mechanical ventilation dependency. Further, RCT is imperative to comprehensively assess the utilization of PGI and PGE1 in treating PH in CDH patients.
PROSPERO Identifier CRD42023438338.
A Comparative Analysis of Traditional and New Construction Methods for External Wall Insulation in Jiangning, Nanjing, China
Authors: Clement Francis Deng , Mehdipour Armin , Shutian Zhou
Published: May 2024

This research conducted in Jiangning, Nanjing, China, aimed to examine the effectiveness of traditional and contemporary construction techniques for external wall insulation. The study compared thermal resistance, indoor air temperature, energy consumption, and potential energy savings. The results showed that new construction methods utilizing fiber-based thermal insulation materials displayed superior performance in various aspects leading to improved thermal insulation properties. Based on the comparative analysis presented in this study, it is suggested that incorporating organic insulation materials into new construction methods for external wall insulation can enhance thermal performance and energy efficiency when compared to traditional approaches. Current energy-saving design standards have been raised by more than 50%, highlighting the growing significance of designing buildings with energy conservation in mind within our country's industrial development context. A newly proposed construction program involving integrated insulation panel composite exterior wall systems demonstrates cost-effectiveness with lower costs per square meter when compared to traditional methods. This study provides an analysis of the thermal performance and energy efficiency associated with both traditional and modern construction methods for external wall insulation specifically within Jiangning, Nanjing area. The investigation highlights the importance of considering varying climatic conditions' impact on thermal performance and retrofitting existing structures for enhanced energy efficiency. It leverages insights from sustainable development studies to promote sustainability in the construction industry while prioritizing public safety and compliance with energy-saving regulations.
Study of plasma-related parameters and self- generated TMF of contact under DB-DC VCB delayed breaking conditions
Authors: Yang Shurui , Huang Chongyang , Shan Zengyu , Li Zhengbo , Cao Yundong
Published: May 2024

Taking the mechanical double-break DC vacuum circuit breaker as the research object, the magnetic field and temperature field distribution between the breaks and the plasma characteristics under the working condition of gap difference caused by actuator dispersion are investigated to explore the difference of arc characteristics between the two breaks with different gaps. Based on the system of equations of Maxwell and magnetohydrodynamic (MHD) equations, a non-simultaneous breaking model of the DB DC VCB is established, and parameters such as magnetic flux density, plasma velocity, inter-contact pressure, and ion and electron temperatures are calculated. The simulation results show that the cathode surface field emission effect is stronger in the small gap break (delayed breaking break). Besides, in the small gap break, the arc temperature in is higher, the rate of decrease of temperature is lower, the electron velocity is higher, the magnetic flux density is lower, the regulatory ability of magnetic field is weaker, and the plasma diffusion speed is slower. In the arc ignition stage, the arc aggregation state duration of small gap break is longer than the normal break, and the arc transition time in small gap break is increased, which means the arc in small gap break get diffusion state later, and it is not conducive to the plasma diffusion and arc energy dissipation. Therefore, the arc energy density between delayed breaking break is greater, the arc morphology transition time is longer, the residual particle concentration after arc extinguishing is higher, and the probability of re-strike breakdown increases with the increase of gap difference. Improving the synchronization of the actuator could improving the breaking ability of DB DC VCB.
Validation of smartwatch electrocardiogram intervals in children compared to standard 12 lead electrocardiograms
Authors: Ernstsson Julia , Svensson Birgitta , Liuba Petru , Weismann Constance G
Published: May 2024

Background/Aim: Lay people are now able to obtain one-lead electrocardiograms (ECG) using smartwatches, which facilitates documentation of arrhythmias. The accuracy of smartwatch derived ECG intervals has not been validated in children though. Home-based monitoring of ECG intervals using a smartwatch could improve monitoring of children, e.g. when taking QTc prolonging medications. The aim of this study was to validate the ECG intervals measured by smartwatch in comparison to standard 12-lead ECGs in children and adolescents.
Methods: Prospective study of children (age 5 - 17 years) at the outpatient clinic of a national pediatric heart center. Patients underwent a smartwatch ECG (ScanWatch, Withings) and a simultaneous standard 12-lead ECG. ECG intervals were measured both automatically and manually from the smartwatch ECG and the 12-lead ECG. Intraclass correlation coefficients and Bland-Altman plots were performed.
Results: 100 patients (54% male, median age 12.9 (IQR 8.7-15.6) were enrolled. The ICC calculated from the automated smartwatch and automated 12-lead ECG were excellent for heart rate (ICC 0.97, p<0.001), good for the PR and QT intervals (ICC 0.86 and 0.8, p<0.001), and moderate for the QRS duration and QTc interval (ICC 0.7 and 0.53, p<0.001). When using manual measurements for the smartwatch ECG, validity was improved for the PR interval (ICC 0.93, p<0.001), QRS duration (ICC 0.92, p<0.001), QT (ICC 0.95, p<0.001) and QTc interval (ICC 0.84, p<0.001).
Conclusion: Automated smartwatch intervals are most reliable measuring the heart rate. The automated smartwatch QTc intervals are less reliable, but this may be improved by manual measurements.
The Child Dental Care Reform in Israel – Service Uptake from 2011 to 2022
Authors: Herman Hagit Domb , Dadosh Hazav , Dekel Dan , Yellon David , Zusman Shlomo Paul , Natapov Lena
Published: May 2024

Background: The 2010 Child Dental Care Reform of the National Health Insurance Law marked a turning point in the Israeli oral healthcare system by establishing Universal Health Coverage of dental care for children. Initially, the reform included children up to age 8 and gradually expanded to age 18 in 2019. The basket of services includes preventive and restorative treatments provided by the four Health Maintenance Organizations (HMO). The aim of this study was to examine the uptake of child dental services during the first decade of the reform.
Methods: A retrospective analysis was conducted to determine the treatment uptake, type and amount of the services delivered based on annual service utilization reports submitted by the HMOs to the Ministry of Health in the years 2011-2022.
Results: The number of insured children increased from 1,546,857 in 2011 to 3,178,238 in 2022. The uptake of dental services gradually increased during the study period with a slight decrease in 2020. The percentage of children who used the services gradually increased from 8% to 33%, with the incremental inclusion of additional age groups. From 2012 onwards the most common treatments provided were preventive, however the single most common treatment was dental restoration. In 2022 35% of the population of Israel was under the age of 18. Out of these, about a third received dental treatment via the HMOs. This is a significant achievement, since before the reform all treatments were paid out-of-pocket. After a short period of increasing uptake, a stable service utilization pattern was evident that can indicate better public awareness and service acceptance.
Conclusion: Although this is a reasonable uptake, additional efforts are required to increase the number of children receiving dental care within the public insurance. Such an effort can be part of a multi-disciplinary approach, in which pediatricians and public health nurses can play a vital role in dental caries prevention, enhancement of awareness and service utilization.
Effectiveness of Diaphragmatic Breathing with Quadriceps Exercises on Maximum Phonation Time, Respiratory function and Muscle Strengthening in Community- Dwelling Elderly
Authors: Prathanee Benjamas , Buakanok Netra , Pumnum Tawitree , Ooppanasak Nantiya , Panyaek Nichanun
Published: May 2024

Most of population in the world recently move to super-aged society. Program of health promotion for community-dwelling elderly requires critical concern. Objectives: The objectives of this study were to compare maximum phonation time (MPT), Maximum counting duration (MCD), Peak expiratory flow rate (PEFR), Maximum inspiratory pressure (MIP), Maximum expiratory pressure (MEP), and quadriceps muscle strengthening before and after breathing with quadriceps exercises. Methods: Twenty- three community-dwelling healthy elderly aged 60–70 years old (mean = 65.52 and standard deviation = 2.41) were enrolled to complete study. Participants did program of breathing with quadriceps exercises twice a day in sitting, standing position and walking for 7 weeks. Results: Median of MPT of /a; u; i:/ before exercises = 8.61–10.14 seconds. Wilcoxon Sign Rank Test was found significant better medians of MPT, MCD, PEFR, MIP, MEP, and quadriceps muscle strength after program. function. Conclusion: Program of breathing with quadriceps exercises could significantly increase MPT, MCD, PEFR, MIP, MEP, and quadriceps muscle strength in community-dwelling healthy elderly within 7 weeks.
Efficacy and Safety Evaluation of Intravenous MiSaver Stem Cell Therapy in Recent Acute Myocardial Infarction: A Retrospective Phase IIa Study
Authors: Liu Jackson , Ueng KwoChang , Tsai ChinFeng , Su Chun-Hung , Chuang YaoTsung
Published: May 2024

Background: Despite advancements in cardiovascular treatments, acute myocardial infarction (AMI) remains a significant health challenge. We aimed to explore the potential of stem cell therapy to improve left ventricular function post-AMI through an open-label, dose-escalating trial. The study aimed to assess the safety and feasibility of intravenous infusion of MiSaver, a prefabricated product of ABO matched allogeneic umbilical cord blood stem cells (USC), in patients following recent AMI.
Methods: Participants were enrolled in cohorts of five, receiving escalating dosages of USC (0.5x10^7, 1.6x10^7, and 5.0x10^7 cells/kg). Infusions were administered 2-5 days post-AMI onset. Due to recruitment challenges during the COVID-19 pandemic, this retrospective analysis was conducted using completed low and middle dosage groups and a control group comprising 20 eligible participants meeting similar inclusion criteria.
Results: The primary analysis focused on safety and adverse events (AEs) over a 12-month observational period in the treatment group. The treatment was well-tolerated, with no AEs directly attributed to MiSaver. Initial analysis of nine participants showed statistically significant improvements in left ventricular ejection fraction (LVEF) from baseline to 12 months post-treatment compared to the control group (p<0.05); however, significance was lost upon inclusion of participant 10. This participant drew attention to the analysis and exhibited unique characteristics, namely the highest body mass index (BMI) and the youngest age among all participants.
Conclusion: This study suggests the potential of MiSaver in enhancing left ventricular function post-AMI. Notably, participants without morbid obesity showed significant recovery in LVEF, suggesting the exclusion of individuals with high BMI in future trials. Larger cohorts and controlled placebo studies are warranted to validate these findings and address trial limitations.
Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline
Authors: Langelier Charles , Lu Dan , Kalantar Katrina , Chu Victoria , Glascock Abigail , Guerrero Estella , Bernick Nina , Butcher Xochitl , Ewing Kirsty , Fahsbender Elizabeth , Holmes Olivia , Hoops Erin , Jones Ann , Lim Ryan , McCanny Suzette , Reynoso Lucia , Rosario Karyna , Tang Jennifer , Valenzuela Omar , Mourani Peter , Pickering Amy , Raphenya Amogelang , Alcock Brian , McArthur Andrew
Published: May 2024

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the CZ ID AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.
Identification of a novel mitophagy-related signature for predicting clinical prognosis and immunotherapy of osteosarcoma
Authors: Xu Peichuan , Zhao Jiangminghao , Zhao Wenrui , Yuan Jinghong , Li Kaihui , Wang Yameng , Hu Yiming , Pan Chongzhi , Pan Huajun , Wu Tianlong , Miao Xinxin , Cheng Xigao
Published: May 2024

Background
Osteosarcoma (OS) is a highly aggressive malignancy characterized by a poor prognosis. Mitochondrial autophagy (mitophagy) has been implicated in tumor initiation, progression, and response to therapy, highlighting it a potential prognostic indicator and therapeutic target in cancers. Despite this, the precise mechanisms underlying mitophagy in osteosarcoma remain enigmatic. This research aims to develop a mitophagy-associated signature to guide therapeutic strategies and prognosis estimations.
Methods
Clinical and transcriptome data for patients with osteosarcoma and skeletal muscle tissue were retrieved from UCSC Xena and GTEx. Mitophagy-related genes (MRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) website. A predictive risk model was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Cox regression analysis. To delve into the fundamental gene expression mechanisms, we employed Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA). Moreover, the different immune-related activities between the two groups were investigated to ascertain the efficacy of immunotherapy. Lastly, the functional analysis of the key risk gene MRAS was carried out via in vitro experiments and a pan-cancer analysis and potential small molecule drugs that may target MRAS were screened through molecular docking.
Results
Based on seven mitophagy-related prognostic gene signatures, osteosarcoma patients were stratified into high- and low-risk categories. The predictive model exhibited strong prognostic capability, as evidenced by Kaplan-Meier analysis, time-dependent AUC, and Nomogram. Notably, compared to the low-risk group, individuals in the high-risk group exhibited lower stromal, immune, and estimate scores.The infiltration of immune cells in high-risk group decreased. Further evidence supporting MRAS's protective role against osteosarcoma was shown in vitro, where upregulating its expression could suppress the proliferation, migration, and invasion of osteosarcoma cells while stimulating their apoptosis. Pan-cancer analysis further demonstrated its role in a variety of tumors.
Conclusion
This study identified a mitophagy-related prognostic signature and elucidated the impact of MRAS on osteosarcoma cells. Consequently, it opened up fresh avenues for clinical prognosis prediction and established a basis for precision therapy in osteosarcoma.
Asthma and risk of gestational diabetes mellitus: a Mendelian randomization study
Authors: huang Yuzhou , Rong Pengfei , Wang Dan , Lu Jianyun
Published: May 2024

Background
Research has uncovered a significant association between asthma and the elevated risk of gestational diabetes mellitus (GDM). Yet, the specific impact of asthma on the occurrence of GDM has not been completely delineated. The objective of this research was to explore the direct impact of asthma on GDM prevalence, employing a two-sample Mendelian randomization (MR) approach.
Methods
This research conducted a two-sample Mendelian randomization analysis utilizing collective data from genome-wide association studies, which were available to the public and concentrated on participants of European descent. The inverse-variance-weighted (IVW) method was adopted as the primary analytic technique. To strengthen the credibility of the findings, additional analytical techniques were employed, such as MR-Egger regression, the weighted median, simple mode, and weighted mode analyses. An extensive array of sensitivity analyses was executed to ensure the reliability of the causal inferences.
Results
The IVW showed that genetically predicted asthma was significantly associated with an increased incidence of GDM(OR = 1.14, 95% CI = 1.04–1.24, p = 0.034).This outcome was also validated by other methods, including the weighted median (OR = 1.15, 95% CI = 1.02–1.30, p = 0.015) and simple mode (OR = 1.34, 95% CI = 1.03–1.73, p = 0.030). No heterogeneity and level pleiotropy were observed in sensitivity analyses.
Conclusions
The results indicate that asthma could be a contributing factor in the onset of GDM, underscoring the need for additional studies to explore the underlying connections between these conditions. It is essential to conduct more research to elucidate the causal relationships that link asthma with the emergence of GDM.
An immortalized porcine mesangial cell line competent for the cultivation of Japanese encephalitis virus
Authors: Xu Shengkui , Zong Shucheng , Liu Xinze , Pan Wen , Guo Fucheng , FU Jinyu , Liu Zhongyin , Xiao Jin
Published: May 2024

Japanese encephalitis virus causes a huge threat to the pig-raising industry and attenuated-live vaccines are widely used to prevent JEV infection. Nowadays, primary hamster kidney cells and Vero cells are mostly used for the propagation of JEV attenuated vaccines. In this research, we constructed porcine-derived-immortalized mesangial cells (PMCs) for JEV cultivation, and their characteristics were also studied. The prepared PMCs were uniform in shape and without variation in chromosome numbers. Furthermore, PMCs showed strong division and proliferation ability, and JEV could replicate efficiently as well causing a cytopathic effect similar to that in Vero cells. The viral tiler results showed that JEV grows faster in PMCs compared with that in Vero cells. Taken together, we generated an immortalized PMC cell line competent for the cultivation of JEV, which has significance for the production of pig JEV attenuated vaccines.
Unraveling the Molecular Mechanisms Underlying Flat Stem Formation in Atractylodes lancea in Response to Phytoplasmas
Authors: Gong Ling , Chen Lei , Huang Xiao , Deng Juan , Wu Xiaoyi , Hu Yating , Jiang Meiling , Yu Kun , Liu Changliu
Published: May 2024

Atractylodes lancea (Thunb.) DC has been widely used as a medicinal herb for centuries. However, long-term artificial cultivation of A. lancea led to serious plant diseases, such as the flat branch disease caused by phytoplasmas. To explore the formation mechanism of flat stems, we measured the changes in physiological and biochemical indicators and related metabolic pathways in stems of A. lancea in response to phytoplasma. After infection by pathogen, significant changes were observed in the content of stress compounds H2O2 and MDA, as well as the activities of antioxidant enzymes APX, POD, PPO, and CAT. The contents of jasmonic acid and zeatin in the flat stem (FS) of A. lancea increased significantly, while auxin content decreased. High-throughput sequencing showed that differentially expressed genes (DEGs) are enriched in hormone biosynthesis, signal transduction, Ca2+ signaling, and other pathways. These results preliminary elucidate the molecular mechanism of flat stem development in A. lancea, providing a foundation for disease prevention in the future.
Multi-scale Interaction Underlying the 2022 Concurrent Extreme Precipitation in Pakistan and Mega Heatwave in Yangtze River Valley
Authors: Ma Qianrong , Sun Yingxiao , Hu Rui , zhu zhiwei , Xiong Kaiguo , Wu Hao , Yan Pengcheng , Feng Guolin
Published: May 2024

Unprecedentedly extreme precipitation occurred in Pakistan (PAK), and mega heat waves persisted along the Yangtze River Valley (YRV) from July to August 2022. Using the advanced multiscale window transform-based canonical transfer attribution framework, we quantitatively delineated multi-scale and inter-scale interactions leading to record-breaking spatially concurrent extremes in 2022 and comprehensively revealed differences in dynamic processes affecting extreme events in July and August. The quasi-stationary window lost the available potential energy (APE), and through APE canonical transfers to the intraseasonal-scale and synoptic-scale windows, the inter-scale dynamic processes and barotropic instability of the basic-scale preserved the concurrent extreme in July. In August, the eruptive high-frequency-scale kinetic energy convergence provided dynamic conditions for the sinking motion of the YRV and its advection to PAK from the Indian Ocean. Consequently, the interaction between high- and low-frequency processes drove atmospheric circulation in summer, but the high-frequency process in August played a vital role in extreme events. Additionally, the heat source in the tropical western-central Pacific is considered one of the key drivers for localized repetitive bursts of energy. This study emphasizes both the interactions between multiple scales of atmospheric dynamics and revealing the driving mechanisms behind the impacts of warming on extreme events, linking the external forcing issue with the free problem of atmospheric internal instability.
Alterations of intrinsic brain activity in subthreshold depression after internet-based cognitive behavioral therapy intervention
Authors: Wang Yu , Ying Yuchen , Zhu Zili , Wang Li , Yang YiLing , Zhang Li , Yu Wenquan , Liang Yichuan , Ji Yunxin , Pan Yuning
Published: May 2024

Background
Subthreshold depression (SD) is a prevalent mental health condition that is recognized as a key precursor to major depressive disorder (MDD) and has a significant negative impact on individuals' quality of life. Internet-based cognitive behavioral therapy (ICBT) is considered an efficacious psychological intervention that enhances access to psychotherapeutic services. Nevertheless, the neuromechanism underlying the effectiveness of ICBT in SD has not been explored until now. This study seeks to investigate the intrinsic alterations in brain activity in SD before and after ICBT intervention using resting-state functional MRI (rs-fMRI) analysis.
Methods
Twenty-five individuals with SD and 25 age- and gender-matched healthy controls (HC) were enrolled in the study. SD received ICBT intervention and underwent MRI scans within 48 hours before and after the intervention, along with clinical assessment scales. HC underwent a single MRI scan at the time of enrollment. Analyses of amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were conducted to assess intrinsic brain activity in all participants. Two-sample t-tests were performed to compare whole-brain differences of ALFF and DC between HC and SD before ICBT intervention, and paired-sample t-tests were employed to examine changes in whole-brain ALFF and DC in SD before and after ICBT intervention. The associations among altered ALFF and DC values and the changes in clinical assessment scores in SD were evaluated by Pearson or Spearman correlation analyses.
Results
Compared to HC, decreased DC in the right precuneus (PCUN) and increased ALFF in the right insula (INS) were found in SD before ICBT intervention. After ICBT intervention, ALFF in the left hippocampus (HIP) was increased, and DC in the right medial and paracingulate gyri (DCG) was reduced in SD. Altered ALFF values in the left HIP showed a negative correlation with the changes in Patient Health Questionnaire-9 Items (PHQ-9) scores, and a positive correlation with the changes in Frequency of Actions and Thoughts Scale in terms of rewarding behaviours (FATS-ReB) scores. Altered DC values in the right DCG positively correlated with the changes in Competencies of Cognitive Therapy Scale-Therapist Report in terms of behavioral activation (CCTS-TR-BhA) scores.
Conclusions
The findings provide new insights into the altered intrinsic brain activities in SD. More importantly, this study demonstrates the potential intrinsic activity changes in brain regions associated with ICBT response to SD, further elucidating the neuropsychological mechanism underlying the efficacy of ICBT.
Trial registration:
This protocol was retrospectively registered at Chinese Clinical Trial Register (ChiCTR) on February 22, 2022, with Identifier: ChiCTR2200056884 (https://www.chictr.org.cn/showproj.html?proj=154448).
Hybrid Metaheuristic Algorithms for Feature Selection in Classification: A Systematic Literature Review
Authors: Othman Manal Mohammed , Ku-Mahamud Ku Ruhana
Published: May 2024

The effectiveness of a machine learning model is significantly impacted by feature selection. Feature selection is one of the most popular and highly effective techniques for eliminating irrelevant and redundant features to enhance the relevance of the collected data and improve the effectiveness of classification tasks. Feature selection is challenging because of the intricate relationship between features and large search space, which grows exponentially with the number of existing features in the original dataset. Metaheuristic algorithms are the most effective techniques for managing feature selection due to their robustness, intelligibility, and effectiveness in solving intricate optimization problems. Recent studies have focused on using hybrid metaheuristics as feature selection approaches. This systematic literature review explores recent studies from 2019 to 2023 that used hybrid metaheuristic algorithms for feature selection in classification. This paper aims to understand the existing hybrid algorithms, the goal of hybridization, the type of hybridization, and their application domains. Moreover, crucial parameters, fitness and transfer functions, initial population method, feature selection approach, classification algorithm, evaluation criteria, and statistical test are also investigated in this paper. A list of 30 relevant papers in line with the topic were extracted and examined to develop new insights in the domain of feature selection in classification. The focus is on a single fitness function (single objective). However, feature selection can be seen as a multi-objective problem, making hybridization in multi-objective feature selection problems a future research work for scholars.
Preoperative severe pain, decreased function, and high anxiety levels increase preoperative anxiety in patients who underwent primary total knee arthroplasty
Authors: Park Ki-Bong , Jeon Young Dae , Kim Sang-Gon , Park Jae-Hwan
Published: May 2024

Patients experience clinically significant anxiety from the time they are recommended to undergo total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of a preoperative intervention regarding anxiety levels in patients undergoing TKA for knee osteoarthritis (OA) and to evaluate whether patient characteristics affect the effectiveness of the intervention according to anxiety level.
This retrospective observational study recruited 89 patients who underwent TKA under general anesthesia for knee OA. The preoperative intervention comprised rehabilitation education and an interview with an orthopedic surgeon regarding surgical preparation status. The State-Trait Anxiety Inventory (STAI) was administered before and after the preoperative intervention.
The mean STAI score significantly improved after the intervention. The proportion of patients with clinically meaningful state anxiety (CMSA) also significantly decreased after the intervention. There were no significant differences in demographic and social factors between the two groups. However, the patients whose CMSA status did not improve experienced severe pain, poor functional scores, and high anxiety scores.
For patients undergoing TKA, the implementation of a patient-specific intervention, which consists of preoperative rehabilitation education and a surgeon interview, helps reduce preoperative anxiety. However, these interventions may not be effective in patients who present with severe pain, poor functional status, or high anxiety levels before surgery. Thus, higher levels of intervention for anxiety may be necessary.
Characteristics and Outcomes in Bladder Leiomyoma Management: A Systematic Review of Case Reports and Case Series from the Past 20 Years
Authors: Prihadi Johannes Cansius , Hengky Antoninus , Lionardi Stevan Kristian , Haruman Sean Peter
Published: May 2024

Introduction
Less than 0.5% of cases are bladder leiomyomas, which are uncommon, non-cancerous growths that originate from the smooth muscle cells of the bladder. The purpose of this review is to compile existing data and present a summary of bladder leiomyomas' characteristics, management, and related outcomes.
Method
Case studies or series describing individuals with bladder leiomyoma who underwent surgery and the results they reported thereafter were included. Four databases were used in our literature search, which was carried out until January 2024: PubMed, Proquest, EBSCOHost, and Google Scholar. We utilized MeSH terms such "leiomyoma," "urinary bladder," and looked for synonyms of "bladder leiomyoma" in free text.
Results
The majority of reported bladder leiomyoma cases were in female accounting for 77.7% of all cases. While symptomatic patients primarily presented with lower urinary tract symptoms (LUTS) (60.7%), hematuria (23.0%), acute urine retention (11.5%), and about 16.4% of cases were incidentally detected. Storage-related symptoms were the most common LUTS (32.8%). Different diagnostic techniques were used, frequently combining CT, MRI, USG, and/or cystoscopy. Bladder leiomyomas were commonly found on left lateral wall (26.4%) and the bladder neck (17.4%). In more than half of the cases (51.2%) the treatment techniques used were transurethral resection (TURBt/TUR). Fifteen out of 121 cases had recurrence or remain symptomatic.
Conclusion
Further investigation is necessary to fully understand the best course of treatment and long-term results for bladder leiomyomas. In particular, prospective trials with bigger participant pools and meticulously controlled factors should be the main emphasis of this research.