bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of the cardiac delirium index by including age, decrease in butyrylcholinesterase actitivity, preoperative HbA1c, and postoperative hemoglobin levels: results of a secondary analysis of a prospective observational study
Authors: Zajonz Thomas S. , Edinger Fabian , Markmann Melanie , Gräb Katrin , Sander Michael , Kunzemann Christian , Koch Christian , Schneck Emmanuel 
Published: December 2024

IntroductionPostoperative delirium (POD) after cardiac surgery significantly affects the perioperative morbidity and mortality. Butyrylcholinesterase (BChE) is an enzyme primarily produced in the liver, which plays a crucial role in the hydrolysis of acetylcholine outside of neuronal synapses, referred to as extraneuronal hydrolysis. The integration of BChE activity into the cardiac delirium (CARDEL) index might increase its predictive power for identifying POD after cardiac surgery. Therefore, the primary aim of this study was to assess the applicability of the CARDEL index and determine whether integrating the BChE activity enables optimization of the predictive model.MethodsThis secondary analysis of a prospective observational study included patients undergoing elective coronary artery bypass graft surgery. BChE activity is expressed in units per liter (U/L), while the BChE drop refers to the percentage decrease in BChE activity from pre- to postoperative levels. POD risk factors were identified using multivariate regression analysis. The predictive power of the CARDEL index and an optimized model including BChE was calculated with receiver operating characteristic (ROC) analysis.ResultsOf 93 included patients, 20 (21.5%) developed POD. Elevated preoperative HbA1c [OR 2.5 (1.2–4.8), p = 0.01], a decrease in BChE activity [%, OR 1.1 (1.0–1.2), p = 0.04], age [1 (0.94–1.1), p = 0.55], and a postoperative hemoglobin change [OR 0.86 (0.78–0.96), p &lt; 0.001] were identified as independent risk factors for POD. While the CARDEL index showed a moderate prediction of POD [AUCROC of 0.74 (0.60–0.87)], the optimization including BChE resulted in a significant prognostic improvement: AUCROC of 0.84 (0.72–0.94, p &lt; 0.001).ConclusionDespite the small size of this derivation cohort, this study identified elevated HbA1c as the strongest risk factor for the development of POD, followed by a decrease in BChE activity, postoperative anemia, and age, respectively. By including these parameters to the CARDEL index, its predictive power for the identification of POD significantly improved in this derivation cohort. Moving forward, integrating these findings into clinical practice could enhance early risk stratification and targeted intervention for patients at high risk of POD. Therefore, further research should evaluate these results in a larger, external cohort.
Body mass index and waist-to-height ratio effect on mortality in non-alcoholic fatty liver: revisiting the obesity paradox
Authors: Jiang Hao , Li Mingkai , Yu Hongsheng , Huang Yinan , Yang Bilan , Wu Bin , Yang Yidong 
Published: December 2024

PurposeEmerging research indicates that individuals with non-alcoholic fatty liver disease (NAFLD) who carry excess weight have similar or even higher survival rates than their normal-weight counterparts. This puzzling “obesity paradox” may be attributed to underlying biases. To explore this phenomenon, we examined data extracted from the third National Health and Nutrition Examination Survey (NHANES) III, which spanned from 1988-1994.MethodsWe specifically targeted participants diagnosed with NAFLD through ultrasound due to fatty liver presence and employed multivariate Cox regression to assess mortality risk associated with body mass index (BMI) and the waist-to-height ratio (WHtR).ResultsOver a median follow-up period of 20.3 [19.9-20.7] years, 1832 participants passed away. The study revealed an intriguing “obesity−survival paradox”, in which individuals classified as overweight (HR 0.926, 95% CI 0.925–0.927) or obese (HR 0.982, 95% CI 0.981–0.984) presented reduced mortality risks compared with those categorized as normal weight. However, this paradox vanished upon adjustments for smoking and exclusion of the initial 5-year follow-up period (HR 1.046, 95% CI 1.044–1.047 for overweight; HR 1.122, 95% CI 1.120–1.124 for obesity class I). Notably, the paradox was less pronounced with the WHtR, which was significantly different only in quartile 2 (HR 0.907, 95% CI 0.906–0.909) than in quartile 1, and was resolved after appropriate adjustments. In particular, when BMI and WHtR were considered together, higher levels of adiposity indicated a greater risk of mortality with WHtR, whereas BMI did not demonstrate the same trend (p &lt;0.05).ConclusionThe “obesity paradox” in NAFLD patients can be explained by smoking and reverse causation. WHtR was a better predictor of mortality than BMI.
Case report: Multiple approach analysis in a case of clinically assessed myotonia congenita
Authors: Lucchiari Sabrina , Fortunato Francesco , Meola Giovanni , Mignarri Andrea , Pagliarani Serena , Corti Stefania , Comi Giacomo P. , Ronchi Dario 
Published: December 2024

Myotonia congenita, both in a dominant (Thomsen disease) and recessive form (Becker disease), is caused by molecular defects in CLCN1 that encodes the major skeletal muscle chloride channel, ClC-1. This channel is important for the normal repolarization of muscle action potentials and consequent relaxation of the muscle, and its dysfunction leads to impaired muscle relaxation after voluntary or evoked contraction and muscle stiffness. More than 300 CLCN1 pathogenic variants have been found in association with congenital myotonia, inherited as recessive or dominant traits (with complete or incomplete penetrance). In this study, we describe the case of a 44-year-old woman complaining of “leg stiffness” since the age of 20 years and presenting with transient muscle weakness, especially after sitting for several minutes, with grip myotonia and feet myotonia, cold-sensitive and warm-up. The strength was normal, but muscle hypertrophy in the lower limbs was evident. EMG myotonia was detected in all explored muscles. The patient’s father had precocious cataract correction but did not show myotonic discharges at EMG. Examination of the patient’s sons (aged 18 years and 12 years) was unremarkable. The patient started treatment with mexiletine, with improvement in grip myotonia and limb stiffness, but it was soon interrupted due to gastrointestinal disturbances. Direct sequencing of CLCN1 identified the previously described heterozygous intronic variant c.1471 + 1G &gt; A, which resulted in the skipping of exon 13 in the CLCN1 muscle transcript. In addition, the rare heterozygous synonymous nucleotide change c.762C &gt; T p.Cys254Cys was identified and predicted to alter physiological splicing. The detection of multiple splicing abnormalities leading to premature termination codons supported the in silico prediction. We developed a Western blot assay to assess the ClC-1 protein in muscle biopsy, and we observed that ClC-1 levels were consistently reduced in the patient’s muscle, supporting the pathogenic behavior of the variants disclosed. Overall, we report a novel case of Becker myotonia and highlight the importance of multiple levels of analysis to achieve a firm molecular diagnosis.
Association between glucose to lymphocyte ratio and prognosis in patients with solid tumors
Authors: Liu Rongqiang , Shen Yankun , Cui Jiahui , Ma Wangbin , Wang Jianguo , Chen Chen , Wang Weixing 
Published: December 2024

BackgroundGlucose-to-lymphocyte ratio (GLR) plays an important role in the prognosis of various tumors. The aim of this study was to comprehensively evaluate the prognostic value of GLR in solid tumors through the meta-analysis.MethodsA comprehensive search of eligible studies was performed by scrutinizing the Pubmed, Embase and Web of science databases until May 30, 2024. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate overall survival (OS), disease-free survival (DFS) and recurrence free survival (RFS).ResultsA total of 22 studies from 14 articles involving 9472 patients were included in the study. The pooled analysis showed that cancer patients with high GLR was significantly associated with unfavorable OS (HR:1.48,95% CI:1.34-1.63) and DFS/RFS (HR:2.20,95% CI:1.66-2.92). Subgroup analysis further showed that high GLR had better predictive value in liver cancer (HR:2.66, 95%CI:1.80-3.93), breast cancer (HR:2.13, 95%CI:1.10-4.13) and pancreatic cancer (HR:1.92, 95%CI:1.30-2.84).ConclusionsGLR can be used as an effective prognostic marker in patients with solid tumors.
NK cells-derived extracellular vesicles potency in the B cell lymphoma biotherapy
Authors: Cecchetti Serena , Federici Cristina , Canese Rossella , Iorio Egidio , Huber Veronica , Pisanu Maria Elena , Chirico Mattea , Iessi Elisabetta , Camerini Serena , Casella Marialuisa , Matteucci Andrea , Macchia Daniele , Spada Massimo , Lugini Luana 
Published: December 2024

IntroductionExtracellular vesicles of Natural Killer cells (NKEV) exert an antitumor effect towards hematopoietic and solid tumors and have an immune modulating effect, suggesting a promising role in immune and biotherapy. In this study, a continuation of our former works, we demonstrated a network by mass spectrometry analysis between NKEV protein cargo and antitumor effects. Human healthy NKEV, both exosomes and microvesicles, have a significant and direct cytotoxic effect against human B cell lymphoma in in vitro and in vivo conditions.MethodsWe isolated extracellular vesicles from in vitro amplified healthy human NK cells and their treatment efficacy was monitored by cytometry analyses, in vivo MRI/MRS measurements, ex vivo MRS analyses and immunohistochemistry.ResultsWe observed a remarkable NKEV cytotoxic effect, mainly by apoptosis, on B cell lymphoma in vitro when exosomes and microvesicles were administered simultaneously. In vivo results showed metabolic alterations in SCID mice xenografts after NKEV treatment, associated with a significant reduction of tumor growth (64%). In the in vivo1H MR spectra we found a significant increase in the tumor lipid/lactate and in taurine signals, both considered as apotosis markers. Ex vivo lymphoma metabolomics revealed a significant increase in fatty acid (FA) pool and decrease in unsaturated and mono-unsaturated FA in treated groups, as compared to control one, thus suggesting an alteration of tumor homeostasis. Immunohistochemistry analyses confirmed the reduction of B-cell lymphoma proliferation rate, as well as the induction of apoptosis following the NKEV treatment. ConclusionsThis study underscore the importance of NKEV as a novel biological acellular tool for B-cell lymphoma treatment, probably having a greater effect on combined treatment regimens. These nanovesicles have an extraordinary potential in innovative cancer immunotherapy, representing a safe and efficient tool naturally circulating in healthy individuals and ready to maintain the immune homeostasis, and therefore a good organism healthy state.
Exploring the heterogeneity of osteosarcoma cell characteristics and metabolic states and their association with clinical prognosis
Authors: Qin Sen , Hu YaoFeng , Deng RuCui , Wang Zhe 
Published: December 2024

BackgroundOsteosarcoma is a malignant tumor originating from mesenchymal bone tissue, characterized by high malignancy and poor prognosis. Despite progress in comprehensive treatment approaches, the five-year survival rate remains largely unchanged, highlighting the need to clarify its underlying mechanisms and discover new therapeutic targets.MethodsThis study utilized RNA sequencing data from multiple public databases, encompassing osteosarcoma samples and healthy controls, along with single-cell RNA sequencing data. Various methods were utilized, such as differential expression analysis of genes, analysis of metabolic pathways, and weighted gene co-expression network analysis (WGCNA), to pinpoint crucial genes. Using this list of genes, we developed and validated a prognostic model that incorporated risk signatures, and we evaluated the effectiveness of the model through survival analysis, immune cell infiltration examination, and drug sensitivity evaluation.ResultsWe analyzed gene expression and metabolic pathways in nine samples using single-cell sequencing data. Initially, we performed quality control and clustering, identifying 21 statistically significant cell subpopulations. Metabolic analyses of these subpopulations revealed heterogeneous activation of metabolic pathways. Focusing on the osteoblastic cell subpopulation, we further subdivided it into six groups and examined their gene expression and differentiation capabilities. Differential expression and enrichment analyses indicated that tumor tissues were enriched in cytoskeletal and structural pathways. Through WGCNA, we identified core genes negatively correlated with four highly activated metabolic pathways. Using osteosarcoma patient data, we developed a risk signature model that demonstrated robust prognostic predictions across three independent cohorts. Ultimately, we performed a thorough examination of the model, which encompassed clinical and pathological characteristics, enrichment analysis, pathways associated with cancer markers, and scores of immune infiltration, highlighting notable and complex disparities between high-risk and low-risk populations.ConclusionThis research clarifies the molecular mechanisms and metabolic features associated with osteosarcoma and how they relate to patient outcomes, offering novel perspectives and approaches for targeted therapy and prognostic assessment in osteosarcoma.
Optimization and design of electromechanical control automation based on dual motor control algorithm
Authors: Lu Wei 
Published: December 2024

IntroductionIn response to the high demand for dynamic characteristics and control in current electromechanical automatic control systems.MethodsThis study first analyzes the dual motor system. A novel electromechanical control automation model based on a dual motor control algorithm is proposed through the control strategy of dual motor backlash elimination and digital proportional integral derivative control algorithm.Results and DiscussionThe results indicated that the optimization of the model had a promoting effect on the control performance of the electromechanical automatic control system. Compared with other popular electromechanical control automation models of the same type, the performance of the research method was the best. During the no-load start-up phase, the maximum tracking error and synchronization error speed of the proposed new electromechanical control automation model showed a significant decreasing trend, with the maximum synchronization error between the two motors being only 0.02%. Under steady-state sudden load, the research model could reach a stable state within 3 s, with errors within ±5%.ConclusionIn summary, combining the dual motor control algorithm with the electromechanical control automation method can provide a theoretical basis and practical guidance for designing and implementing efficient dual motor electromechanical control systems.
Targeted dual-receptor phage cocktail against Cronobacter sakazakii: insights into phage-host interactions and resistance mechanisms
Authors: Kim Seongok , Son Bokyung , Kim Yeran , Kim Hyeongsoon , Nam Gahyeon , Shin Hakdong , Ryu Sangryeol 
Published: December 2024

IntroductionCronobacter sakazakii is a notorious foodborne pathogen, frequently contaminating powdered infant formula and causing life-threatening diseases in infants. The escalating emergence of antibiotics-resistant mutants has led to increased interest in using bacteriophage as an alternative antimicrobial agent.MethodsTwo phages, CR8 and S13, were isolated from feces and soil samples and their morphology, physiology, and genomics were characterized. Phage receptor was determined using deletion mutants lacking flgK, rfaC, fhuA, btuB, lamb, or ompC genes, followed by complementation. Phage-resistant mutants were analyzed for phenotypic changes and fitness trade-offs using motility assays and Caco-2 cell invasion models.ResultsCR8 and S13 were identified as members of Caudoviricetes. Phage CR8 and phage S13 utilize flagella and LPS, respectively, to adhere to host cells. Bacterial challenge assay demonstrated delayed emergence of the resistant mutant as well as stronger lytic activity of a phage cocktail consisting of CR8 and S13 than the single phage treatment. Phenotypic analysis of the phage cocktail resistant strain, designated as CSR strain, revealed that the resistance resulted from the impaired receptor proteins for phage, such as defects in motility and alteration in LPS structure. CSR strain exhibited significant attenuation in invading human intestinal epithelial Caco-2 cells compared to WT cells.ConclusionThis study demonstrates that the development of the phage cocktail targeting distinct host receptors can serve as a promising antimicrobial strategy to effectively control C. sakazakii.
Emamectin·chlorfenapyr-induced fatal leukoencephalomyelopathy with delayed hyperthermia: insecticide endanger public safety
Authors: Li Xun , Yang Yun , Zhang Yajing , Zhang Xuebin , Zhao Na , Yue Wei 
Published: December 2024

BackgroundEmamectin·chlorfenapyr is a compound comprising chlorfenapyr and emamectin benzoate that is widely used in agriculture. Chlorfenapyr toxicity has been verified in animals; however, its true mechanism and progression in humans remain to be elucidated. Cases of emamectin·chlorfenapyr poisoning are seldom.Case presentationWe present a case of a 65-year-old female who attempted suicide by consuming 30 g of 9.5% chlorfenapyr and 0.5% emamectin benzoate 14 days before admission to our hospital. Laboratory tests revealed extremely high creatinine kinase levels upon admission. Magnetic resonance imaging revealed diffuse and symmetric T2 hyperintensities in the entire white matter tract of the brain and spinal cord, and cytological smears of the cerebrospinal fluid showed abnormal lymphocyte aggregation. The patient died 19.5 h after admission owing to cardiopulmonary arrest and hyperthermia.ConclusionFurther research is needed on how to perform flow cytometry in patients with emamectin·chlorfenapyr intoxication, and to elucidate the immunological mechanism underlying the inflammatory response caused by emamectin·chlorfenapyr and provide new insights into antidote development.
Predictive model for PSA persistence after radical prostatectomy using machine learning algorithms
Authors: Du Haotian , Wang Guipeng , Yan Yongchao , Li Shengxian , Yang Xuecheng 
Published: December 2024

ObjectiveTo evaluate the efficacy of a machine learning model for predicting prostate-specific antigen (PSA) persistence after radical prostatectomy (RP).MethodsData from 470 patients who underwent RP at the Affiliated Hospital of Qingdao University from January 2018 to June 2021 were retrospectively analyzed. Ten risk factors, including age, body mass index (BMI), preoperative PSA, biopsy Gleason score, total prostate specific antigen density (PSAD), clinical tumor stage, clinical lymph node status, seminal vesicle invasion, capsular invasion and positive surgical margin, were included in the analysis. The data were randomly divided into a training set and a test set at a ratio of 7:3, and seven different machine learning algorithms were compared. The confusion matrix, receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic performance of the model, and the random forest algorithm found to be the optimal prediction model.ResultsIn the entire cohort, 142 (30.21%) patients developed PSA persistence. Based on all included risk factors, the random forest model had the best effect among the seven models, with an AUC of 0.8607 in the training set and 0.8011 in the test set. The feature importance results showed that capsular invasion, positive surgical margin, preoperative PSA and biopsy Gleason score were the four most important risk factors for PSA persistence after RP.ConclusionThe Random Forest algorithm performed excellently in this study and can be used to construct a predictive model for PSA persistence. By incorporating clinical data from the Asian region and exploring the risk factors for PSA persistence, this study contributes to the existing research and aids clinicians in assessing the risk of PSA persistence occurrence, enabling timely treatment planning and improving patient prognosis.
Voriconazole: a review of adjustment programs guided by therapeutic drug monitoring
Authors: Jiang Li , Lin Zhiqiang 
Published: December 2024

ObjectivesExploring adjustments to the voriconazole dosing program based on therapeutic drug monitoring results to implement individualized therapy.MethodsPubMed and Embase were systematically searched to obtain study about voriconazole dose adjustment program guided by therapeutic drug monitoring. Quality evaluation and summarization of the obtained studies were performed to obtain program adjustments for voriconazole under therapeutic drug monitoring.ResultsA total of 1,356 and 2,979 studies were searched on PubMed and Embase, respectively, and after removing irrelevant and duplicated studies, a total of 25 studies were included. A loading dose of 5 mg/kg q12 h or 200 mg q12 h and a maintenance dose of 50 mg q12 h or 100 mg q24 h is recommended for patients with Child-Pugh C. And in patients with Child-Pugh C, CYP2C19 genotype had no significant effect on voriconazole blood concentrations. Recommendations for presenting dosing programs based on different CYP2C19 genotypes are inconsistent, and genetic testing is not routinely recommended prior to dosing from a pharmacoeconomic perspective. Additionally, in adult patients, if the voriconazole trough concentration is subtherapeutic, the voriconazole dose should be increased by 25%∼50%. If the voriconazole trough concentration is supratherapeutic,the voriconazole dose should be decreased by 25%∼50%. If a drug-related adverse event occurs, hold 1 dose, decrease subsequent dose by 50%.In pediatric patients, if the voriconazole trough concentration is subtherapeutic, increase the voriconazole dose by 1∼2 mg/kg or increase the voriconazole dose by 50%. If the voriconazole trough concentration is supratherapeutic, reduce the voriconazole dose by 1 mg/kg or hold 1 dose, and decrease the subsequent dose by 25%.ConclusionIt is recommended that all patients on voriconazole should have their initial dosing program selected on the basis of their hepatic function or other influencing factors (e.g., pathogens, infections, C-reactive protein, albumin, or obesity), and that therapeutic concentrations should be achieved through appropriate dosage adjustments guided by therapeutic drug monitoring. Routine genetic testing for voriconazole application in patients is not considered necessary at this time. However, there has been a great deal of research and partial consensus on individualized dosing of voriconazole, but there are still some critical issues that have not been resolved.