bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of new Schiff bases of the disalicylic acid scaffold as DNA gyrase and topoisomerase IV inhibitors endowed with antibacterial properties
Authors: Al-Wahaibi Lamya H. , Mahmoud Mohamed A. , Alzahrani Hayat Ali , Abou-Zied Hesham A. , Gomaa Hesham A. M. , Youssif Bahaa G. M. , Bräse Stefan , Rabea Safwat M. 
Published: June 2024

DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been identified; however, none have been effective in the market. For the first time, we developed a series of disalicylic acid methylene/Schiff bases hybrids (5a-k) to act as antibacterial agents targeting DNA gyrase and topoisomerase IV. The findings indicated that the new targets 5f-k exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria, with efficacy ranging from 75% to 115% of the standard ciprofloxacin levels. Compound 5h demonstrated the greatest efficacy compared to the other compounds tested, with minimum inhibitory concentration (MIC) values of 0.030, 0.065, and 0.060 μg/mL against S. aureus, E. coli, and P. aeruginosa. 5h had a MIC value of 0.050 μg/mL against B. subtilis, which is five times less potent than ciprofloxacin. The inhibitory efficacy of the most potent antibacterial derivatives 5f, 5h, 5i, and 5k against E. coli DNA gyrase was assessed. The tested compounds demonstrated inhibitory effects on E. coli DNA gyrase, with IC50 values ranging from 92 to 112 nM. These results indicate that 5f, 5h, 5i, and 5k are more effective than the reference novobiocin, which had an IC50 value of 170 nM. Compounds 5f, 5h, 5i, and 5k were subjected to additional assessment against E. coli topoisomerase IV. Compounds 5h and 5i, which have the highest efficacy in inhibiting E. coli gyrase, also demonstrated promising effects on topoisomerase IV. Compounds 5h and 5i exhibit IC50 values of 3.50 µM and 5.80 µM, respectively. These results are much lower and more potent than novobiocin’s IC50 value of 11 µM. Docking studies demonstrate the potential of compound 5h as an effective dual inhibitor against E. coli DNA gyrase and topoisomerase IV, with ADMET analysis indicating promising pharmacokinetic profiles for antibacterial drug development.
Synthesis and full-spectrum-responsive photocatalytic activity from UV/Vis to near-infrared region of S-O decorated YMnO3 nanoparticles for photocatalytic degradation of ibuprofen
Authors: Feng Zixia 
Published: June 2024

The oxalic acid complexation method and sulfuric acid heat treatment method were used to synthesize the YMnO3 (YMO) and YMO-SO42- (YMO-SO) photocatalysts. The YMO-SO photocatalyst maintained the crystal structure of YMO, but the particle size increased slightly and the optical band gap decreased significantly. The YMO-SO photocatalyst demonstrates a wide range of light absorption capabilities, covering ultraviolet, visible and near-infrared light. The photocatalytic activity of YMO-SO was investigated with ibuprofen as the target pollutant. The YMO-SO photocatalyst exhibits high ultraviolet (UV), visible and near-infrared photocatalytic activity. Experiments with different environmental parameters confirmed that the best catalyst content was 1 g/L, the best drug concentration was 75 mg/L and the best pH value was 7. The capture experiment, free radical detection experiment and photocatalytic mechanism analysis confirmed that the main active species of YMO-SO photocatalyst were hole and superoxide free radical.
Utilization of the Shensheng-Piwen changed medicinal powder extracts combines metal-organic frameworks as an antibacterial agent
Authors: Jin Haiqun , Zhang Xiujun , Ma Xiaoqing , Meng Xin , Lin Zhenguang , Li Xiaoyuan , Hu Guojie , Chen Yao 
Published: June 2024

IntroductionWidespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs.MethodsThis study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts.ResultsMetabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against S. aureus, with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of S. aureus revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of S. aureus. Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect.DiscussionIn conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against S. aureus infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.
Impacts of COVID-19 pandemic on culture-proven sepsis in neonates
Authors: Yang Xiaofeng , Ren Luxin , Gong Min , Lu Yanhong , Ding Xin 
Published: June 2024

ObjectiveTo assess the effects of COVID-19 pandemic on the epidemiology of neonatal sepsis and the antibiotic resistance profiles of pathogens involved.MethodsThis retrospective cohort study analyzed infants diagnosed with culture-proven sepsis at the neonatal department of a tertiary children’s hospital in East China from January 2016 to December 2022. We compared the clinical and microbiological characteristics of neonatal sepsis cases between the pre-pandemic Phase I (2016–2019) and during the COVID-19 pandemic Phase II (2020–2022).ResultsA total of 507 infants with 525 sepsis episodes were included, with 343 episodes in Phase I and 182 in Phase II. The incidence of early-onset sepsis (EOS) was significantly lower during Phase II (p &lt; 0.05). Infants in Phase II had lower gestational ages and birth weights compared to Phase I. Clinical signs such as mottled skin, severe anemia, thrombocytopenia were more prevalent in Phase II, alongside a higher incidence of complications. Notably, necrotizing enterocolitis (NEC) (p &lt; 0.05) and meningitis (p &lt; 0.1) occurred more frequently during Phase II. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the predominant pathogens isolated from infants of death and cases with complications. A significant decrease in the proportion of K. pneumoniae was observed in Phase II, alongside increased antibiotic resistance in both E. coli and K. pneumoniae. The period of the COVID-19 pandemic (Phase II) was identified as an independent risk factor for complications in infants with neonatal sepsis.ConclusionCOVID-19 pandemic response measures correlated with a decrease in EOS and an increase in neonatal sepsis complications and antibiotic resistance.
Anti-chlamydial activity of vaginal fluids: new evidence from an in vitro model
Authors: Morselli Sara , Ceccarani Camilla , Djusse Marielle Ezekielle , Laghi Luca , Camboni Tania , Consolandi Clarissa , Foschi Claudio , Severgnini Marco , Marangoni Antonella 
Published: June 2024

IntroductionWe assessed the in vitro anti-chlamydial activity of fresh vaginal secretions, deciphering the microbial and metabolic components able to counteract Chlamydia trachomatis viability.MethodsForty vaginal samples were collected from a group of reproductive-aged women and their anti-chlamydial activity was evaluated by inhibition experiments. Each sample underwent 16S rRNA metabarcoding sequencing to determine the bacterial composition, as well as 1H-NMR spectroscopy to detect and quantify the presence of vaginal metabolites.ResultsSamples characterized by a high anti-chlamydial activity were enriched in Lactobacillus, especially Lactobacillus crispatus and Lactobacillus iners, while not-active samples exhibited a significant reduction of lactobacilli, along with higher relative abundances of Streptococcus and Olegusella. Lactobacillus gasseri showed an opposite behavior compared to L. crispatus, being more prevalent in not-active vaginal samples. Higher concentrations of several amino acids (i.e., isoleucine, leucine, and aspartate; positively correlated to the abundance of L. crispatus and L. jensenii) lactate, and 4-aminobutyrate were the most significant metabolic fingerprints of highly active samples. Acetate and formate concentrations, on the other hand, were related to the abundances of a group of anaerobic opportunistic bacteria (including Prevotella, Dialister, Olegusella, Peptostreptococcus, Peptoniphilus, Finegoldia and Anaerococcus). Finally, glucose, correlated to Streptococcus, Lachnospira and Alloscardovia genera, emerged as a key molecule of the vaginal environment: indeed, the anti-chlamydial effect of vaginal fluids decreased as glucose concentrations increased.DiscussionThese findings could pave the way for novel strategies in the prevention and treatment of chlamydial urogenital infections, such as lactobacilli probiotic formulations or lactobacilli-derived postbiotics.
Efficacy and safety evaluation of Allisartan Isoproxil in patients with hypertension: a meta-analysis
Authors: Zhao Fengfeng , Liu Yihua , Chen Liang 
Published: June 2024

ObjectiveThis study aimed to evaluate the effectiveness and safety of Allisartan Isoproxil in the management of hypertension.MethodsA comprehensive search was conducted across both English and Chinese databases, including the Cochrane Library, Embase, PubMed, Web of Science, Chinese Journal Full Text Database (CNKI), Wanfang Digital Periodical Full Text Database, and VIP Chinese Periodical Database (VIP), up to March 24, 2024. Randomized controlled trials (RCTs) investigating alisartan axetil for hypertension management were selected. Literature quality was assessed, and data were extracted for meta-analysis using Stata 15.1 software. The quality of evidence for outcome indicators was evaluated using the GRADE system level.ResultsSix RCTs involving 767 participants were included. Meta-analysis revealed that, compared to placebo, the Allisartan Isoproxil group exhibited a significant reduction in systolic blood pressure (SBP) [WMD = −8.08, 95% CI (−11.81, 4.10), p = 0.000] and brachial-ankle pulse wave velocity (baPWV) [SMD = −0.69, 95% CI (−1.17, 0.20), p = 0.006]. However, the reduction in diastolic blood pressure (DBP) was not statistically significant [WMD = −5.48, 95% CI (−11.07, 0.10), p = 0.054]. Additionally, compared to calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB), Allisartan Isoproxil did not significantly affect SBP [WMD = 0.20, 95% CI (−3.71, 4.10), p = 0.921] or DBP [WMD = 0.16, 95% CI (−2.11, 2.43), p = 0.891]. Allisartan Isoproxil demonstrated superior effects in increasing nitric oxide (NO) levels and decreasing endothelin (ET) levels compared to control groups [WMD = 9.56, 95% CI (6.42, 12.71), p = 0.000], [WMD = −7.42, 95% CI (−11.13, −3.71), p = 0.000], and showed a higher effective control rate of blood pressure [RR = 1.26, 95% CI (1.13, 1.41), p = 0.000]. Subgroup analysis did not reveal significant differences. Regarding safety, there were no statistically significant differences in adverse events between the Allisartan Isoproxil group and the control groups [RR = 0.99, 95% CI (0.74, 1.32), p = 0.928], and no fatal adverse events were reported.ConclusionAllisartan Isoproxil is effective in reducing SBP and baPWV, increasing NO, decreasing ET, and achieving a higher control rate of blood pressure in patients with essential hypertension. These benefits are achieved with minimal adverse reactions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023467869, identifier PROSPERO CRD42023467869.
Exploring the causal relationship between immune cell and all-cause heart failure: a Mendelian randomization study
Authors: Li Jixu , Liu Liangliang , Luo Qiuyan , Zhou Weiyue , Zhu Yao , Jiang Weimin 
Published: June 2024

Background and objectivesHeart failure (HF) is a disease with numerous genetic and environmental factors that affect it. The results of previous studies indicated that immune phenotypes are associated with HF, but there have been inconclusive studies regarding a causal relationship. Therefore, Mendelian randomization (MR) analyses were undertaken to confirm the causal connections between immune phenotypes and HF, providing genetic evidence supporting the association of immune cell factors with HF risk.MethodsWe selected instrumental variables that met the criteria based on data from the results of genome-wide association studies (GWAS) of immune phenotype and all-cause HF. An evaluation of the causal association between 731 immune cell factors and HF risk was carried out using the inverse variance weighted (IVW), MR-Egger regression (MR-Egger), and weighted median (WM) analysis methods. To determine the horizontal pleiotropy, heterogeneity, and stability of the genetic variants, the MR-Egger intercept test, Cochran's Q test, MR-PRESSO, and leave-one-out sensitivity analysis were performed.ResultsMR principal method (IVW) analysis showed that a total of 38 immune cell-related factors were significantly causally associated with HF. Further analyses combining three methods (IVW, MR-Egger and WME) showed that six exposure factors significantly associated with heart failure, as shown below. The effect of Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell on heart failure was positive. Whereas, a reverse effect was observed for CD14+ CD16+ monocyte% monocyte.ConclusionWe investigated the causal relationship between immune phenotypes and all-cause HF. According to the results, Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell aggravate HF, and the risk of HF is decreased by CD14+ CD16+ monocyte% monocyte. These phenotypes may serve as new biomarkers, providing new therapeutic insights for the prevention and treatment of all-cause HF.
Experience with a novel high frequency optical coherence tomography device for intracoronary imaging: a case series
Authors: Garin Dorian , Cook Stéphane , Togni Mario , Meier Pascal , Wenaweser Peter , Puricel Serban , Arroyo Diego 
Published: June 2024

IntroductionIntravascular imaging, especially optical coherence tomography (OCT), has significantly improved percutaneous coronary intervention (PCI), yet its routine clinical application faces challenges. This case series introduces the Gentuity® High-Frequency Optical Coherence Tomography (HF-OCT), a novel device designed to enhance intracoronary imaging with a significantly faster pullback and smaller catheter size, potentially offering enhanced navigability in complex lesions. We aimed to assess the image quality of Gentuity® HF-OCT in complex vessel conditions, as well as presenting a case series to illustrate the application of the device in various clinical scenarios.MethodsIn this case series, we included all patients who underwent intracoronary HF-OCT imaging at our center. The primary endpoint was image quality assessed by clear image length (CIL). Image quality was assessed in relation to (1) lesion severity assessed by minimum lumen area (MLA); (2) vessel size, differentiating between larger (diameter ≥ 4 mm) and smaller vessel segments; (3) pre- vs. post-PCI conditions, and (4) vessel tortuosity, categorized into none, moderate, and severe.ResultsTwenty-four HF-OCT runs from 14 patients were included. No significant differences in CIL were observed across lesion severity terciles (p = 0.449), between small and large vessel segments [mean CIL% difference 1.3%; confidence interval (CI), −9.3 to 11.8; p = 0.802], and pre- vs. post-PCI conditions (mean CIL difference −3.9 mm; CI, −14.0 to 6.1; p = 0.373). Vessel tortuosity significantly impacted image quality, with clear reductions in CIL observed in cases of moderate (74.8; CI, 73.5 to 76.0; vs. 63.9; CI, 56.2 to 71.5; p = 0.043) and severe tortuosity (74.8; CI, 73.5 to 76.0; vs. 65.0; CI, 62.1 to 67.9; p = 0.002) compared to vessels with no tortuosity. Overall, the HF-OCT demonstrated excellent catheter deliverability and crossability, with very satisfactory image quality and no significant adverse events.ConclusionThe Gentuity® HF-OCT is a new OCT device capable of navigating both small- and large-diameter vessels, with similar image quality, but vessel tortuosity seems to have an impact on image quality. It appears to be as usable as conventional OCT for pre-PCI diagnosis and OCT-guided PCI, potentially bringing additional benefits in terms of deliverability, lesion crossover and ease of use in routine clinical practice.
Blood urea nitrogen to creatinine ratio is associated with in-hospital mortality in critically ill patients with venous thromboembolism: a retrospective cohort study
Authors: Puri Anju , Giri Mohan , Huang Huanhuan , Zhao Qinghua 
Published: June 2024

BackgroundThe relationship between the blood urea nitrogen to creatinine ratio (BCR) and the risk of in-hospital mortality among intensive care unit (ICU) patients diagnosed with venous thromboembolism (VTE) remains unclear. This study aimed to assess the relationship between BCR upon admission to the ICU and in-hospital mortality in critically ill patients with VTE.MethodsThis retrospective cohort study included patients diagnosed with VTE from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was in-hospital mortality. Univariate and multivariate logistic regression analyses were conducted to evaluate the prognostic significance of the BCR. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cut-off value of BCR. Additionally, survival analysis using a Kaplan–Meier curve was performed.ResultsA total of 2,560 patients were included, with a median age of 64.5 years, and 55.5% were male. Overall, the in-hospital mortality rate was 14.6%. The optimal cut-off value of the BCR for predicting in-hospital mortality in critically ill VTE patients was 26.84. The rate of in-hospital mortality among patients categorized in the high BCR group was significantly higher compared to those in the low BCR group (22.6% vs. 12.2%, P &lt; 0.001). The multivariable logistic regression analysis results indicated that, even after accounting for potential confounding factors, patients with elevated BCR demonstrated a notably increased in-hospital mortality rate compared to those with lower BCR levels (all P &lt; 0.05), regardless of the model used. Patients in the high BCR group exhibited a 77.77% higher risk of in-hospital mortality than those in the low BCR group [hazard ratio (HR): 1.7777; 95% CI: 1.4016–2.2547].ConclusionAn elevated BCR level was independently linked with an increased risk of in-hospital mortality among critically ill patients diagnosed with VTE. Given its widespread availability and ease of measurement, BCR could be a valuable tool for risk stratification and prognostic prediction in VTE patients.
Case report: The success of empagliflozin therapy for glycogen storage disease type 1b
Authors: Klinc Ana , Groselj Urh , Mlinaric Matej , Homan Matjaz , Markelj Gasper , Mezek Novak Ajda , Sirca Campa Andreja , Sikonja Jaka , Battelino Tadej , Zerjav Tansek Mojca , Drole Torkar Ana 
Published: June 2024

IntroductionGlycogen storage disease type 1b (GSD-1b) is characterized by neutropenia and neutrophil dysfunction generated by the accumulation of 1,5-anhydroglucitol-6-phosphate in neutrophils. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, facilitate the removal of this toxic metabolite and ameliorate neutropenia-related symptoms, including severe infections and inflammatory bowel disease (IBD). Our case series presents the treatment of three pediatric GSD-1b patients with empagliflozin over a follow-up of three years; the most extended reported follow-up period to date.Cases descriptionA retrospective analysis of empagliflozin treatment of three pediatric GSD-1b patients (two male and one female; ages at treatment initiation: 4.5, 2.5 and 6 years) was performed. Clinical and laboratory data from a symmetrical period of up to three years before and after the therapy introduction was reported. Data on the clinical course of the treatment, IBD activity, the need for antibiotic treatment and hospitalizations, neutrophil count and function, and markers of inflammation were assessed. Prior the introduction of empagliflozin, patients had recurrent oral mucosa lesions and infections, abdominal pain, and anemia. During empagliflozin treatment, the resolution of aphthous stomatitis, termination of abdominal pain, reduced frequency and severity of infections, anemia resolution, increased appetite, and improved wound healing was observed in all patients, as well as an increased body mass index in two of them. In a patient with IBD, long-term deep remission was confirmed. An increased and stabilized neutrophil count and an improved neutrophil function enabled the discontinuation of G-CSF treatment in all patients. A trend of decreasing inflammation markers was detected.ConclusionsDuring the three-year follow-up period, empagliflozin treatment significantly improved clinical symptoms and increased the neutrophil count and function, suggesting that targeted metabolic treatment could improve the immune function in GSD-1b patients.