bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two cinnamoyl hydroxamates as potential quorum sensing inhibitors against Pseudomonas aeruginosa
Authors: Pan Deng , Wu Hua , Li Jun-Jian , Wang Bo , Jia Ai-Qun 
Published: August 2024

IntroductionPseudomonas aeruginosa is a ubiquitous pathogen that causes various infectious diseases through the regulation of quorum sensing (QS). The strategy of interfering with the QS systems of P. aeruginosa, coupled with a reduction in the dosage of conventional antibiotics, presents a potential solution to treating infection and mitigating antibiotic resistance. In this study, seven cinnamoyl hydroxamates were synthesized to evaluate their inhibitory effects on QS of P. aeruginosa. Among these cinnamic acid derivatives, we found cinnamoyl hydroxamic acid (CHA) and 3-methoxy-cinnamoyl hydroxamic acid (MCHA) were the two most effective candidates. Furtherly, the effect of CHA and MCHA on the production of virulence factors and biofilm of P. aeruginosa were evaluated. Ultimately, our study may offer promising potential for treating P. aeruginosa infections and reducing its virulence.MethodsThe disc diffusion test were conducted to evaluate inhibitory effects on QS of seven cinnamoyl hydroxamates. The influence of CHA and MCHA on the production of virulence and flagellar motility of P. aeruginosa was furtherly explored. Scanning electron microscopy (SEM) experiment were conducted to evaluate the suppression of CHA and MCHA on the formed biofilm of P. aeruginosa. RT-qPCR was used to detect rhlI, lasA, lasB, rhlA, rhlB, and oprL genes in P. aeruginosa. In silico docking study was performed to explore the molecular mechanism of CHA and MCHA. The synergistic effects of CHA with gentamicin were detected on biofilm cell dispersal.ResultAfter treatment of CHA or MCHA, the production of multiple virulence factors, including pyocyanin, proteases, rhamnolipid, and siderophore, and swimming and swarming motilities in P. aeruginosa were inhibited significantly. And our results showed CHA and MCHA could eliminate the formed biofilm of P. aeruginosa. RT-qPCR revealed that CHA and MCHA inhibited the expression of QS related genes in P. aeruginosa. Molecular docking indicated that CHA and MCHA primarily inhibited the RhlI/R system in P. aeruginosa by competing with the cognate signaling molecule C4-HSL.Additionally, CHA exhibited potent synergistic effects with gentamicin on biofilm cell dispersal.DiscussionP. aeruginosa is one of the most clinically and epidemiologically important bacteria and a primary cause of catheter-related urinary tract infections and ventilator-associated pneumonia. This study aims to explore whether cinnamoyl hydroxamates have inhibitory effects on QS. And our results indicate that CHA and MCHA, as two novel QSIs, offer promising potential for treating P. aeruginosa infections and reducing its virulence.
Development of a multienzyme isothermal and lateral flow dipstick combination assay for the rapid detection of goose astrovirus II
Authors: Zhu Yinchu , Chen Liu , Xu Xin , Ye Weicheng , Ni Zheng , Huo Suxin , Hua Jionggang , Yun Tao , Yao Huochun , Wang Hongyu , Zhang Cun 
Published: August 2024

IntroductionGoose astrovirus (GAstV) is a newly emerging pathogen that is currently widespread among geese, causing visceral gout and leading to substantial gosling mortalities, posing a severe threat to the waterfowl industry. GAstV II is the predominant epidemic strain, characterized by its high morbidity and mortality rate. Consequently, there is an urgent necessity to develop an effective diagnostic approach to control the dissemination of GAstV II, particularly in clinical farms with limited laboratory resources.MethodsIn this study, a novel multi-enzyme isothermal rapid amplification (MIRA) and lateral flow dipstick (LFD) combined assay was developed. Different primers designed specific targeting a highly conserved region within the viral RdRp gene for the detection of GAstV II. Primers optimized and MIRA-LFD assay analyzed its performance regarding limits of detection, specificity, and efficiency of detection.ResultsThe developed MIRA amplification is conducted at a constant temperature and accomplished within 10 minutes. Subsequent naked-eye observation of the LFD strips merely takes 5 minutes. The established MIRA-LFD method exhibits high specificity, with no cross-reaction with other pathogens and attains a detection sensitivity of 1 copy/μl, which is consistent with the reverse transcription quantitative PCR (RT-qPCR) assay. Further evaluation with clinical samples indicates that the accuracy of this MIRA-LFD method correlates well with RT-qPCR for the detection of GAstV II. ConclusionIn summary, the convenience, sensitivity, and rapidity of this newly developed detection method offer a significant advantage for on-site diagnosis of GAstV II.
Effect of astragalus injection on left ventricular remodeling in HFmrEF: a systematic review and meta-analysis
Authors: Han Xu , Huang Lumei , Li Geng , Mou Xinglang , Cheng Caihong 
Published: August 2024

ObjectivesThe aim of this meta-analysis is to evaluate the effect of astragalus injection (AI) on left ventricular remodeling (LVR) in patients with heart failure with mildly reduced ejection fraction (HFmrEF).MethodsThe randomized controlled trials (RCTs) of AI in treating HFmrEF were retrieved from 8 major English and Chinese electronic databases, up until November 30, 2023. To evaluate the methodological quality of the included studies, the Cochrane bias risk tool and the Modified Jadad Scale were employed. Stata 17.0 software was utilized for statistical analysis, sensitivity analysis, and assessment of publication bias.ResultsTen RCTs with 995 patients (562 males and 433 females) were identified. Meta-analysis indicated that compared to conventional treatment (CT), AI significantly improved LVR, specifically increasing left ventricular ejection fraction (LVEF, MD = 4.56, 95% CI: 3.68–5.44, p &lt; 0.00001), decreasing left ventricular end-diastolic volume (LVEDV, MD = −7.89, 95% CI: −11.13 to −4.64, p &lt; 0.00001), left ventricular end-diastolic diameter (LVEDD, MD = −4.18, 95% CI: −5.79 to −2.56, p &lt; 0.00001), left ventricular end-systolic volume (LVESV, MD = −8.11, 95% CI: −11.79 to −4.43, p &lt; 0.00001), and left ventricular end-systolic diameter (LVESD, MD = −3.42, 95% CI: −4.90 to −1.93, p &lt; 0.00001). AI also improved clinical efficacy (RR = 4.62, 95% CI: 3.11–6.88, p &lt; 0.00001), reduced N-terminal pro-brain natriuretic peptide (NT-pro BNP, MD = −27.94, 95% CI: −43.3 to −12.36) level, without increasing the incidence of adverse reactions (RR = 1.60, 95% CI: 0.59–4.29, p = 0.35). Sensitivity analysis confirmed the reliability of the merged results, and Begg's and Egger's tests showed no significant publication bias.ConclusionThe systematic review and meta-analysis revealed that combining AI with CT improves LVR without increasing adverse events in HFmrEF patients. However, caution is needed in interpreting the results due to limited evidence. Future high-quality RCTs are needed to support these conclusions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42022347248].
Application of gene expression programing in predicting the concentration of PM2.5 and PM10 in Xi’an, China: a preliminary study
Authors: Wang Xu , Zhang Kai , Han Peishan , Wang Meijia , Li Xianjun , Zhang Yaqiong , Pan Qiong 
Published: August 2024

Introduction: Traditional statistical methods cannot find quantitative relationship from environmental data.Methods: We selected gene expression programming (GEP) to study the relationship between pollutant gas and PM2.5 (PM10). They were used to construct the relationship between pollutant gas and PM2.5 (PM10) with environmental monitoring data of Xi’an, China. GEP could construct a formula to express the relationship between pollutant gas and PM2.5 (PM10), which is more explainable. Back Propagation neural networks (BPNN) was used as the baseline method. Relevant data from January 1st 2021 to April 26th 2021 were used to train and validate the performance of the models from GEP and BPNN.Results: After the models of GEP and BPNN constructed, coefficient of determination and RMSE (Root Mean Squared Error) are used to evaluate the fitting degree and measure the effect power of pollutant gas on PM2.5 (PM10). GEP achieved RMSE of [8.7365–14.6438] for PM2.5; RMSE of [13.2739–45.8769] for PM10, and BP neural networks achieved average RMSE of [13.8741–34.7682] for PM2.5; RMSE of [29.7327–52.8653] for PM10. Additionally, experimental results show that the influence power of pollutant gas on PM2.5 (PM10) situates between −0.0704 and 0.6359 (between −0.3231 and 0.2242), and the formulas are obtained with GEP so that further analysis become possible. Then linear regression was employed to study which pollutant gas is more relevant to PM2.5 (PM10), the result demonstrates CO (SO2, NO2) are more related to PM2.5 (PM10).Discussion: The formulas produced by GEP can also provide a direct relationship between pollutant gas and PM2.5 (PM10). Besides, GEP could model the trend of PM2.5 and PM10 (increase and decrease). All results show that GEP can be applied smoothly in environmental modelling.
Deciphering breast cancer prognosis: a novel machine learning-driven model for vascular mimicry signature prediction
Authors: Li Xue , Li Xukui , Yang Bin , Sun Songyang , Wang Shu , Yu Fuxun , Wang Tao 
Published: August 2024

BackgroundIn the ongoing battle against breast cancer, a leading cause of cancer-related mortality among women globally, the urgent need for innovative prognostic markers and therapeutic targets is undeniable. This study pioneers an advanced methodology by integrating machine learning techniques to unveil a vascular mimicry signature, offering predictive insights into breast cancer outcomes. Vascular mimicry refers to the phenomenon where cancer cells mimic blood vessel formation absent of endothelial cells, a trait associated with heightened tumor aggression and diminished response to conventional treatments.MethodsThe study’s comprehensive analysis spanned data from over 6,000 breast cancer patients across 12 distinct datasets, incorporating both proprietary clinical data and single-cell data from 7 patients, accounting for a total of 43,095 cells. By employing an integrative strategy that utilized 10 machine learning algorithms across 108 unique combinations, the research scrutinized 100 existing breast cancer signatures. Empirical validation was sought through immunohistochemistry assays, alongside explorations into potential immunotherapeutic and chemotherapeutic avenues.ResultsThe investigation successfully identified six genes related to vascular mimicry from multi-center cohorts, laying the groundwork for a novel predictive model. This model outstripped the prognostic accuracy of traditional clinical and molecular indicators in forecasting recurrence and mortality risks. High-risk individuals identified by our model faced worse outcomes. Further validation through IHC assays in 30 patients underscored the model’s extensive applicability. Notably, the model unveiled varying therapeutic responses; low-risk patients might achieve greater benefits from immunotherapy, whereas high-risk patients demonstrated a particular sensitivity to certain chemotherapies, such as ispinesib.ConclusionsThis model marks a significant step forward in the precise evaluation of breast cancer prognosis and therapeutic responses across different patient groups. It heralds the possibility of refining patient outcomes through tailored treatment strategies, accentuating the potential of machine learning in revolutionizing cancer prognosis and management.
Measuring calf circumference in frail hospitalized older adults and prediction of in-hospital complications and post-discharge mortality
Authors: Canonico Silvia , Ottaviani Silvia , Tagliafico Luca , Casabella Andrea , Signori Alessio , Ponzano Marta , Marelli Cristina , Nencioni Alessio , Monacelli Fiammetta 
Published: August 2024

BackgroundSarcopenia, characterized by muscle mass, strength, and performance decline, significantly impacts outcomes in older adults. This study aims to assess the predictive value of calf circumference (CC), in conjunction with SARC-F and hand grip, concerning in-hospital complications and post-discharge mortality among hospitalized frail older adults.MethodsA cohort of 158 hospitalized patients aged over 65 years underwent Comprehensive Geriatric Assessment and sarcopenia screening, including CC measurement. Multivariable regression analyses, adjusted for confounders, were conducted to assess predictive associations.ResultsThe study cohort, comprising 53% males with a median age of 86 years, exhibited significant sarcopenia prevalence based on SARC-F (85% indicating sarcopenia), hand grip strength (probable sarcopenia in 77% of males and 72% of females), and CC (sarcopenia in 83%). Multivariate analysis, adjusting for age, sex, Clinical Frailty Scale (CFS), and Mini Nutritional Assessment-Short Form (MNA-SF), demonstrated associations of CC and SARC-F with in-hospital complications, while CC also showed a significant association with reduced risks of in-hospital mortality (OR 0.441, 95% CI 0.257 to 0.754, p = 0.003) and 90-day mortality (OR 0.714, 95% CI 0.516 to 0.988, p = 0.043).ConclusionThis study provides insights into the predictive accuracy of sarcopenia screening tools on mortality in real-world hospitalized older adults with frailty. Notably, CC emerges as a robust predictor of mortality outcomes. Further research is warranted to validate and elucidate the respective contributions of CC and frailty to mortality in vulnerable populations.
Trends in the market for drug delivery devices categorized as combination drugs and medical devices and regulatory challenges for autoinjectors in Japan
Authors: Mochizuki Makiko , Maeda Hideki 
Published: August 2024

BackgroundAlthough a variety of drug delivery devices have been launched in recent years, few studies have comprehensively investigated the market trends of combination drugs and medical devices approved or certified in Japan and the regulatory challenges related to their approval. Among the drug delivery devices, autoinjectors are more convenient than traditional prefilled syringes and are designed with safety features to prevent needlestick accidents, allowing self-injection by patients. Therefore, autoinjectors have been incorporated into the treatment of various diseases and have shown significant growth among drug delivery devices.AimThis study aimed to investigate the market trends of combination drugs approved in Japan, especially those with autoinjector formulations, and to explore the challenges in the regulatory aspects of combination drugs.MethodsInformation on the number of marketed drugs and medical devices was obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) database using specific definitions. We looked at the annual changes in the number of drug delivery devices approved and certified as combination drugs or medical devices and the number of canceled certifications. We also examined the classification and main certification criteria for Japanese medical device nomenclature.ResultsThe study suggested that the number of combination drugs with autoinjector formulations is increasing, replacing previously approved or certified pen-type medication injectors. Moreover, 53% of all drug products were approved for autoinjector formulations after the initial authorization approval in Japan, and more than half of them obtained approval for additional formulations for autoinjectors within five years of the initial authorization approval, with the largest number of cases obtaining approval for additional formulations two years later.ConclusionThe lack of clear regulatory requirements for autoinjectors may lead to confusion among applicants. Furthermore, there are challenges in filing regulatory applications, thus hindering the rapid launch of combination drug-utilizing devices with superior usability.
The association between rs6859 in NECTIN2 gene and Alzheimer’s disease is partly mediated by pTau
Authors: Rajendrakumar Aravind Lathika , Arbeev Konstantin G. , Bagley Olivia , Yashin Anatoliy I. , Ukraintseva Svetlana 
Published: August 2024

IntroductionEmerging evidence suggests a connection between vulnerability to infections and Alzheimer’s disease (AD). The nectin cell adhesion molecule 2 (NECTIN2) gene coding for a membrane component of adherens junctions is involved in response to infections, and its single nucleotide polymorphism (SNP) rs6859 was significantly associated with AD risk in several human cohorts. It is unclear, however, how exactly rs6859 influences the development of AD pathology. The aggregation of hyperphosphorylated tau protein (pTau) is a key pathological feature of neurodegeneration in AD, which may be induced by infections, among other factors, and potentially influenced by genes involved in both AD and vulnerability to infections, such as NECTIN2.Materials and methodsWe conducted a causal mediation analysis (CMA) on a sample of 708 participants in the Alzheimer’s disease Neuroimaging Initiative (ADNI). The relationship between rs6859 and Alzheimer’s disease (AD), with AD (yes/no) as the outcome and pTau-181 levels in the cerebrospinal fluid (CSF) acting as a mediator in this association, was assessed. Adjusted estimates from the probit and linear regression models were used in the CMA model, where an additive model considered an increase in dosage of the rs6859 A allele (AD risk factor).ResultsThe increase in dose of allele A of the SNP rs6859 resulted in about 0.144 increase per standard deviation (SD) of pTau-181 (95% CI: 0.041, 0.248, p &lt; 0.01). When included together in the probit model, the change in A allele dose and each standard deviation change in pTau-181 predicted 6.84% and 9.79% higher probabilities for AD, respectively. In the CMA, the proportion of the average mediated effect was 17.05% and was higher for the risk allele homozygotes (AA), at 19.40% (95% CI: 6.20%, 43.00%, p &lt; 0.01). The sensitivity analysis confirmed the evidence of a robust mediation effect.ConclusionThis study reported a new potential causal relationship between pTau-181 and AD. We found that the association between rs6859 in the NECTIN2 gene and AD is partly mediated by pTau-181 levels in CSF. The rest of this association may be mediated by other factors. Our finding sheds light on the complex interplay between genetic susceptibility, protein aggregation, and neurodegeneration in AD. Further research, using other biomarkers, is needed to uncover the remaining mechanisms of the association between the NECTIN2 gene and AD.
Effects of auricular stimulation on weight- and obesity-related parameters: a systematic review and meta-analysis of randomized controlled clinical trials
Authors: Hua Kevin , Usichenko Taras , Cummings Mike , Bernatik Miriam , Willich Stefan N. , Brinkhaus Benno , Dietzel Joanna 
Published: August 2024

BackgroundOver the last three decades, the number of randomized controlled trials (RCTs) using stimulation of auricular vagal sensory nerves by means of electrical stimulation, auricular acupuncture, or acupressure to support weight loss has increased markedly. This systematic review focuses on the effects of auricular stimulation (AS) on anthropometric parameters and obesity-related blood chemistry.Methods and analysisThe following databases were searched until November 2021: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Database. Data collection and analysis were conducted by two reviewers independently. Quality and risk assessment of included studies was performed using the risk of bias tool of the Cochrane Handbook, and the meta-analysis of the effect of the most frequently assessed biomarkers was conducted using the statistical software RevMan.ResultsThe full texts of 1,274 studies were screened; 22 contained data on obesity-related outcomes, and 15 trials with 1,333 patients were included in the meta-analysis. The overall quality of the included trials was moderate. AS significantly reduced body mass index (BMI) (mean difference (MD) = −0.38 BMI points, 95% CI (−0.55 to −0.22), p &lt; 0.0001), weight (MD = −0.66 kg, 95% CI (−1.12 to −0.20), p = 0.005), waist circumference (MD = −1.44 cm, 95% CI (−2.69 to −0.20), p = 0.02), leptin, insulin, and HOMA insulin resistance compared to controls. No significant reduction was found in body fat, hip circumference, ratio of waist/hip circumference, cholesterol, LDL, triglycerides, adiponectin, ghrelin, and glucose levels. The AS was safe throughout the trials, with only minor adverse reactions.ConclusionThe study results suggest that a reduction of weight and BMI can be achieved by AS in obese patients; however, the size of the effect does not appear to be of clinical relevance. The effects might be underestimated due to active sham trials.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231885.
Association of gut microbiota with lactose intolerance and coeliac disease: a two-sample Mendelian randomization study
Authors: Han Zongze , Ran Ying , Li Jiwen , Zhang Xue , Yang Hui , Liu Jiangpeng , Dong Shijing , Jia Hao , Yang Zhen , Li Yanni , Guo Liping , Zhou Simin , Bao Suriguge , Yuan Wei , Wang Bangmao , Zhou Lu 
Published: August 2024

Background and objectivesLactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease.Materials and methodsThis study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane’s Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods.ResultsBy employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study.ConclusionThis study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.