bluuebunny/crossref_metadata_2025_split huggingface dataset:
EBF1 is a potential biomarker for predicting progression from mild cognitive impairment to Alzheimer's disease: an in silico study
Authors: Ju Yanxiu , Li Songtao , Kong Xiangyi , Zhao Qing 
Published: September 2024

IntroductionThe prediction of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is an important clinical challenge. This study aimed to identify the independent risk factors and develop a nomogram model that can predict progression from MCI to AD.MethodsData of 141 patients with MCI were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We set a follow-up time of 72 months and defined patients as stable MCI (sMCI) or progressive MCI (pMCI) according to whether or not the progression of MCI to AD occurred. We identified and screened independent risk factors by utilizing weighted gene co-expression network analysis (WGCNA), where we obtained 14,893 genes after data preprocessing and selected the soft threshold β = 7 at an R2 of 0.85 to achieve a scale-free network. A total of 14 modules were discovered, with the midnightblue module having a strong association with the prognosis of MCI. Using machine learning strategies, which included the least absolute selection and shrinkage operator and support vector machine-recursive feature elimination; and the Cox proportional-hazards model, which included univariate and multivariable analyses, we identified and screened independent risk factors. Subsequently, we developed a nomogram model for predicting the progression from MCI to AD. The performance of our nomogram was evaluated by the C-index, calibration curve, and decision curve analysis (DCA). Bioinformatics analysis and immune infiltration analysis were conducted to clarify the function of early B cell factor 1 (EBF1).ResultsFirst, the results showed that 40 differentially expressed genes (DEGs) related to the prognosis of MCI were generated by weighted gene co-expression network analysis. Second, five hub variables were obtained through the abovementioned machine learning strategies. Third, a low Montreal Cognitive Assessment (MoCA) score [hazard ratio (HR): 4.258, 95% confidence interval (CI): 1.994–9.091] and low EBF1 expression (hazard ratio: 3.454, 95% confidence interval: 1.813–6.579) were identified as the independent risk factors through the Cox proportional-hazards regression analysis. Finally, we developed a nomogram model including the MoCA score, EBF1, and potential confounders (age and gender). By evaluating our nomogram model and validating it in both internal and external validation sets, we demonstrated that our nomogram model exhibits excellent predictive performance. Through the Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes Genomes (KEGG) functional enrichment analysis, and immune infiltration analysis, we found that the role of EBF1 in MCI was closely related to B cells.ConclusionEBF1, as a B cell-specific transcription factor, may be a key target for predicting progression from MCI to AD. Our nomogram model was able to provide personalized risk factors for the progression from MCI to AD after evaluation and validation.
Serum IRAK3 may serve as a prognostic biomarker in acute supratentorial intracerebral hemorrhage: findings from a prospective observational cohort study
Authors: Ma Yijun , Wang Jun , Tang Chao , Li Wei , Lv Xuan , Zhu Suijun 
Published: September 2024

BackgroundInterleukin-1 receptor-associated kinase 3 (IRAK3) modulates neuroinflammation. This study aimed to determine the prognostic role of serum IRAK3 in acute intracerebral hemorrhage (ICH).MethodsIn this prospective observational cohort study, 152 patients with supratentorial ICH, along with 63 healthy controls, were recruited. Serum IRAK3 levels were measured at the time of enrollment for controls, at admission for all patients, and on poststroke days 1, 3, 5, 7, 10, and 15 in a subset of 63 patients. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Poststroke 6-month modified Rankin Scale (mRS) scores were registered, with scores of 3–6 representing a poor prognosis. Multivariate models were established to investigate severity correlation and prognosis association.ResultsSerum IRAK3 levels were significantly elevated at the admission of patients, peaked at day 1, plateaued at day 3, gradually declined until day 15, and were substantially higher over the first 15 days poststroke than in controls. Admission serum IRAK3 levels were independently associated with NIHSS scores, hematoma volume, and 6-month mRS scores in a multivariate linear regression model. They were linearly correlated with the risk of poor prognosis in a restricted cubic spline analysis and were independently predictive of poor prognosis in a binary logistic regression model. Additionally, they demonstrated strong prognostic ability in the receiver operating characteristic curve analysis. Using subgroup analysis, no interactions were found between admission serum IRAK3 levels and some routine variables, such as age, gender, hypertension, and diabetes mellitus. Moreover, the model combining admission serum IRAK3, NIHSS scores, and hematoma volume demonstrated stability and clinical value in calibration and decision curve analyses.ConclusionA significant increase in serum IRAK3 levels during the early phase after ICH, strongly correlated with disease severity, is independently associated with a poor 6-month prognosis, establishing serum IRAK3 as a valuable prognostic biomarker for ICH.
Mendelian randomization analyses explore the effects of micronutrients on different kidney diseases
Authors: Shi Chengdong , Cao Hongliang , Zeng Guoqiang , Wu Hao , Wang Yuantao 
Published: September 2024

BackgroundThe impact of micronutrients, including vitamins and minerals, on different kidney diseases has been reported in some observational studies; however, their causal relationship remains uncertain. We aimed to ascertain the causal genetic relationships between micronutrients and different kidney diseases using the Mendelian randomization (MR) method.MethodsInstrumental variables (IVs) for genetically predicting calcium (Ca), iron (Ir), Zinc (Zn), selenium (Se), copper (Cu), vitamin D (Vit D), and vitamin C (Vit C) levels in humans were obtained, and a bidirectional two-sample MR was used to examine potential associations between the levels of these seven micronutrients and the risk of seven different kidney diseases including hypertensive renal disease, diabetic nephropathy, IgA nephropathy, membranous nephropathy, cystic nephropathy, chronic kidney disease (CKD), and chronic tubulo-interstitial nephritis. Five different MR analyses were conducted, with the main method being the inverse variance-weighted (IVW) method. Moreover, sensitivity analyses were performed to assess heterogeneity and potential pleiotropy.ResultsThe IVW method revealed that Ca levels were associated with a decreased risk of hypertensive renal disease (OR = 0.61, 95% CI: 0.40–0.93, p-value = 0.022), and Se levels were associated with a decreased risk of hypertensive renal disease (OR = 0.72, 95% CI: 0.53–0.99, p-value = 0.040), diabetic nephropathy (OR = 0.83, 95% CI: 0.73–0.93, p-value = 0.002), and CKD (OR = 0.87, 95% CI: 0.77–0.99, p-value = 0.028). Conversely, Vit D levels were associated with an increased risk of polycystic kidney disease (OR = 1.76, 95% CI: 1.15–2.69, p-value = 0.0095). In addition, no potential causal relationship was found between vitamin C levels, iron levels, zinc levels, and copper levels and different kidney diseases. Meanwhile, inverse Mendelian randomization showed no potential causal relationship between different chronic kidney diseases and micronutrients. The Cochrane’s Q test, MR-Egger regression, and MR-PRESSO did not suggest heterogeneity and pleiotropy, providing evidence of the validity of the MR estimates.ConclusionOur results indicate a cause-and-effect connection between micronutrients and certain kidney diseases, but additional study is required to provide more conclusive evidence. This research has the potential to assist clinicians in managing the consumption of specific micronutrients among individuals with chronic kidney diseases, as well as in promoting disease prevention among both healthy populations and those who are susceptible to chronic underlying conditions.
Association of COX-inhibitors with cancer patients’ survival under chemotherapy and radiotherapy regimens: a real-world data retrospective cohort analysis
Authors: Flausino Lucas E. , Ferreira Isabella N. , Tuan Wen-Jan , Estevez-Diz Maria Del Pilar , Chammas Roger 
Published: September 2024

IntroductionWe conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy.MethodsThe study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period.ResultsUse of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits’ risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes.DiscussionSelective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.
Aspirin reduces the mortality risk of patients with community-acquired pneumonia: a retrospective propensity-matched analysis of the MIMIC-IV database
Authors: Wang Guangdong , Sun Jiaolin , Zhang Yaxin , Wang Na , Liu Tingting , Ji Wenwen , Lv Lin , Yu Xiaohui , Cheng Xue , Li Mengchong , Hu Tinghua , Shi Zhihong 
Published: September 2024

BackgroundCommunity-acquired pneumonia (CAP) is a common infectious disease characterized by inflammation of the lung parenchyma in individuals who have not recently been hospitalized. It remains a significant cause of morbidity and mortality worldwide. Aspirin is a widely used drug, often administered to CAP patients. However, the benefits of aspirin remain controversial.ObjectiveWe sought to determine whether aspirin treatment has a protective effect on the outcomes of CAP patients.MethodsWe selected patients with CAP from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) balanced baseline differences. A multivariate Cox regression model assessed the relationship between aspirin treatment and 28-day mortality.ResultsA total of 3,595 patients were included, with 2,261 receiving aspirin and 1,334 not. After PSM, 1,219 pairs were matched. The 28-day mortality rate for aspirin users was 20.46%, lower than non-users. Multivariate Cox regression indicated aspirin use was associated with decreased 28-day mortality (HR 0.75, 95% CI 0.63–0.88, p &lt; 0.001). No significant differences were found between 325 mg/day and 81 mg/day aspirin treatments in terms of 28-day mortality, hospital mortality, 90-day mortality, gastrointestinal hemorrhage, and thrombocytopenia. However, intensive care unit (ICU) stay was longer for the 325 mg/day group compared to the 81 mg/day group (4.22 vs. 3.57 days, p = 0.031).ConclusionAspirin is associated with reduced 28-day mortality in CAP patients. However, 325 mg/day aspirin does not provide extra benefits over 81 mg/day and may lead to longer ICU stays.
Additional effects of herbal medicine combined with bisphosphonates for primary osteoporosis: a systematic review and meta-analysis
Authors: Yoo Young-Seo , Kim Min-Gyeong , Park Hee-Joo , Chae Min-Young , Choi Yu-Jin , Oh Chae-Kun , Son Chang-Gue , Lee Eun-Jung 
Published: September 2024

BackgroundOsteoporosis (OP) is a significant medical issue associated with population aging. Recent research on herbal medicines (HMs) for OP has been increasing, with these therapies sometimes used in conjunction with bisphosphonates (BPs), the standard treatment for OP. We conducted a systematic review and meta-analysis to evaluate the effects of combining HMs with BPs on improving bone mineral density (BMD) in patients with primary OP.MethodsWe searched nine databases—PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Wanfang, KISS, Kmbase, Science On, and Oasis—up to 31 August 2023. We selected randomized controlled trials (RCTs) comparing BMD between HMs plus BPs and BPs alone in primary OP. A meta-analysis with BMD as the primary outcome was performed using RevMan version 5.4. Study quality and evidence certainty were assessed through Cochrane’s risk of bias2 and GRADE.ResultsOut of 43 RCTs involving 4,470 participants (mean age 65.8 ± 6.6 years), 35 RCTs with 3,693 participants were included in the meta-analysis. The combination of HMs and BPs was found to be more effective in improving BMD compared to BPs alone, with improvements of 0.10 g/cm2 at the lumbar spine (33 RCTs, 95% CI: 0.07–0.12, p &lt; 0.001, I2 = 93%) and 0.08 g/cm2 at the femoral neck (20 RCTs, 95% CI: 0.05–0.12, p &lt; 0.001, I2 = 94%), though this result was associated with high heterogeneity, high risk of bias, and very low certainty of evidence.ConclusionOur data suggest the possibility that combining HMs with BPs may improve BMD in primary OP more effectively than using BPs alone. However, the results should be interpreted with caution due to the high heterogeneity and low quality of the studies included in the review. Therefore, further well-designed RCTs are needed to confirm these findings.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023392139.
Quantitative pulmonary pharmacokinetics of tetrandrine for SARS-CoV-2 repurposing: a physiologically based pharmacokinetic modeling approach
Authors: Wang Furun , Dong Liuhan , Hu Juanwen , Yang Shijie , Wang Lingchao , Zhang Zhiwei , Zhang Wenpeng , Zhuang Xiaomei 
Published: September 2024

Tetrandrine (TET) has been traditionally used in China as a medication to treat silicosis and has recently demonstrated anti-SARS-CoV-2 potential in vitro. By recognizing the disparity between in vitro findings and in vivo performance, we aimed to estimate the free lung concentration of TET using a physiologically based pharmacokinetic (PBPK) model to link in vitro activity with in vivo efficacy. Comparative pharmacokinetic studies of TET were performed in rats and dogs to elucidate the pharmacokinetic mechanisms as well as discern interspecies variations. These insights facilitated the creation of an animal-specific PBPK model, which was subsequently translated to a human model following thorough validation. Following validation of the pharmacokinetic profile from a literature report on single oral dosing of TET in humans, the plasma and lung concentrations were predicted after TET administration at approved dosage levels. Finally, the antiviral efficacy of TET in humans was assessed from the free drug concentration in the lungs. Both in vivo and in vitro experiments thus confirmed that the systemic clearance of TET was primarily through hepatic metabolism. Additionally, the lysosomal capture of basic TET was identified as a pivotal factor in its vast distribution volume and heterogeneous tissue distribution, which could modulate the absorption dynamics of TET in the gastrointestinal tract. Notably, the PBPK-model-based unbound lung concentration of TET (1.67–1.74 μg/mL) at the recommended clinical dosage surpassed the in vitro threshold for anti-SARS-CoV-2 activity (EC90 = 1.52 μg/mL). Thus, a PBPK model was successfully developed to bridge the in vitro activity and in vivo target exposure of TET to facilitate its repurposing.
Individualized multi-modal MRI biomarkers predict 1-year clinical outcome in first-episode drug-naïve schizophrenia patients
Authors: Zhang Aoxiang , Yao Chenyang , Zhang Qian , Zhao Ziyuan , Qu Jiao , Lui Su , Zhao Youjin , Gong Qiyong 
Published: September 2024

BackgroundAntipsychotic medications offer limited long-term benefit to about 30% of patients with schizophrenia. We aimed to explore the individual-specific imaging markers to predict 1-year treatment response of schizophrenia.MethodsStructural morphology and functional topological features related to treatment response were identified using an individualized parcellation analysis in conjunction with machine learning (ML). We performed dimensionality reductions using the Pearson correlation coefficient and three feature selection analyses and classifications using 10 ML classifiers. The results were assessed through a 5-fold cross-validation (training and validation cohorts, n = 51) and validated using the external test cohort (n = 17).ResultsML algorithms based on individual-specific brain network proved more effective than those based on group-level brain network in predicting outcomes. The most predictive features based on individual-specific parcellation involved the GMV of the default network and the degree of the control, limbic, and default networks. The AUCs for the training, validation, and test cohorts were 0.947, 0.939, and 0.883, respectively. Additionally, the prediction performance of the models constructed by the different feature selection methods and classifiers showed no significant differences.ConclusionOur study highlighted the potential of individual-specific network parcellation in treatment resistant schizophrenia prediction and underscored the crucial role of feature attributes in predictive model accuracy.
Abdominal impacts of handlebar injuries in the PIPER child model: a prevention study
Authors: Arneitz Christoph , Erlinger Nico , Klug Corina , Senica Simone Oliver , Kuenzer Thomas , Spitzer Peter , Schalamon Georg , Schalamon Johannes 
Published: September 2024

AimAnalysis of data from bicycle accidents reveals that handlebar impacts are a significant cause of injury, particularly among children. Despite existing safety regulations, such as helmet requirements, little attention is given to abdominal injuries. The aim of this study is to investigate the influence of handlebar ends on abdominal loading during bicycle crashes.MethodsThis study delves into the impact of five different handlebar designs on abdominal injuries during bicycle crashes, using finite element simulations with detailed Human Body Models (HBMs) of a six-year-old child (PIPER child model, Version 0.99.0). Four impact locations were identified in the injury scenario, selected according to the anatomical location of the most commonly injured organs, liver, pancreas, spleen and abdomen.ResultsGrip design features, such as shape and rigidity, significantly influence injury outcomes. Grips designed specifically for children demonstrate superior performance in reducing abdominal loading and injury metrics compared to standard grips. The highest injury potential was seen in a damaged handlebar end.ConclusionThese findings underscore the importance of improved handlebar designs and standardized safety measures, especially for children. Implementation of such measures could mitigate the significant health and economic burden associated with handlebar-related injuries and enhance overall bicycle safety for children.
Association between weight-adjusted waist circumference index and depression in older patients with hypertension: a study based on NHANES 2007–2016
Authors: Niu Yi , Sun Yuqin , Xie Yijie , Yu Shun 
Published: September 2024

ObjectiveOur aim was to assess the relationship between weight-adjusted waist circumference index (WWI) and the prevalence of depression in older adult hypertensive patients in the United States.MethodsWe selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2016 and used logistic regression analyses, subgroup analyses, and dose–response curves to assess the associations between the WWI index and the prevalence of depression in older hypertensive patients with age, sex, and BMI.ResultsA total of 4,228 participants aged ≥60 years with hypertension were included in our study; 364 patients were assessed for depression. After correction for confounders, each unit increase in WWI increased the risk of depression in older hypertensive patients by 19% (OR = 1.19, 95% CI: 0.99, 1.43). Dose–response curves showed that the WWI index was positively associated with the prevalence of depression in older hypertensive patients when the WWI index was ≥11.6. Based on subgroup analyses, this association was particularly pronounced in individuals ≥70 years of age, women, and individuals with a BMI of 25 or greater.ConclusionHigher WWI scores were positively associated with the prevalence of depression in older hypertensive patients and correlated with gender, age and BMI. This is notable, although a causal relationship cannot be established at this time.