bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive list of preventative migraine headache medications without significant drug–drug interactions
Authors: Dave Jay , Hakkinen Ian , Zhang Pengfei 
Published: December 2024

Background/objectivePreventive medications are crucial in migraine prevention. In cases of refractory migraine headaches, multiple medications may be required. We seek to identify a comprehensive list of preventive migraine headache medications that can be used as two, three, and four drug combinations without drug–drug interactions.MethodsWe compiled a list of prevention medications from Szperka et al.’s “Migraine Care in the Era of COVID-19” as well as American Headache Society’s 2018 and 2021 “Consensus Statements on Integrating New Migraine Treatments into Clinical Practice.” We obtained all possible two to four combinations of prevention medications through this list. We then filtered out all combinations containing at least one interaction based on DrugBank database and also identified least to most interacting medications.ResultsA total of 26 unique prevention medications are identified. This results in a total of 325 combinations of two preventives, 2,600 combinations of three preventives, and 14,950 combinations of four preventives. There are a total of 124, 146, and 0 non-interacting two, three, and four preventive combinations, respectively. All except 16 combinations of pick-twos can be placed within a pick-three combinations. The resulting distinct non-interacting medications can be represented by a condensed list of 162 unique combinations of medications. CGRP antagonists, Botulinum toxin A, melatonin, and candesartan are least interacting.ConclusionThis list of migraine preventive medications without drug–drug interactions is a useful tool for clinicians seeking to manage refractory headaches more effectively by implementing an evidence-based polypharmacy.
Effects of transcranial direct current stimulation on modulating executive functions in healthy populations: a systematic review and meta-analysis
Authors: You Guopeng , Pan Xinliang , Li Jun , Zhao Shaocong 
Published: December 2024

BackgroundConventional research has asserted that cognitive function, particularly, response inhibition, is closely related to the inferior frontal cortex (IFC), dorsolateral prefrontal cortex (DLPFC), or orbital frontal cortex (OFC), which belong to the prefrontal cortex (PFC). Different targets of anodal or cathodal transcranial direct current stimulation (a-tDCS or c-tDCS) would affect the experimental results, but the stimulation of the same brain target would produce inconsistent findings.PurposeThis study aimed to investigate the effects of a-tDCS and c-tDCS applied over the PFC for healthy populations on reactive and proactive control process compared with sham or no tDCS conditions, as assessed using the Stop-signal task (SST) and Go/NoGo (GNG) task performance.MethodsThis systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Search was conducted on Web of Science, Google Scholar, PubMed, Elsevier, Scopus, and Science Direct until March 2024. Studies that assessed the inhibitory control in SST or/and GNG tasks were included to achieve a homogenous sample.ResultsFourteen studies were included for meta-analyses, which were performed for two outcome measures, namely, stop-signal reaction time (SSRT) and commission error (CE) rate. A-tDCS and c-tDCS over the PFC had significant ergogenic effects on SST performance (mean difference = −17.03, 95% CI [−24.62, −9.43], p &lt; 0.0001; mean difference = −15.19, 95% CI [−19.82, −10.55], p &lt; 0.00001), and that of a-tDCS had a positive effect on GNG task performance (mean difference = −1.42, 95% CI [−2.71, −0.14], p = 0.03).ConclusionThis review confirmed the engagement of PFC tDCS in reactive and proactive inhibitory processes. Future research should increase sample size and implement personalized stimulus protocols.
Mapping the structure of biomarkers in autism spectrum disorder: a review of the most influential studies
Authors: Jin Fang , Wang Zhidan 
Published: December 2024

BackgroundAutism spectrum disorder is a distinctive developmental condition which is caused by an interaction between genetic vulnerability and environmental factors. Biomarkers play a crucial role in understanding disease characteristics for diagnosis, prognosis, and treatment. This study employs bibliometric analysis to identify and review the 100 top-cited articles’ characteristics, current research hotspots and future directions of autism biomarkers.MethodsA comprehensive search of autism biomarkers studies was retrieved from the Web of Science Core Collection database with a combined keyword search strategy. A comprehensive analysis of the top 100 articles was conducted with CiteSpace, VOSviewer, and Excel, including citations, countries, authors, and keywords.ResultsThe top 100 cited studies were published between 1988 and 2021, with the United States led in productivity. Core biomarkers such as genetics, children, oxidative stress, and mitochondrial dysfunction are well-established. Potential trends for future research may include brain studies, metabolomics, and associations with other psychiatric disorders.ConclusionThis pioneering bibliometric analysis provides a comprehensive compilation of the 100 most-cited studies on autism, which not only offers a valuable resource for doctors, and researchers but shedding insights into current shortcomings and future endeavors. Future research should prioritize the application of emerging technologies for biomarkers, longitudinal study of biomarkers, and specificity of autism biomarkers to advance the precision of ASD diagnosis and treatment.
Enzymatically hydrolyzed diet improves growth performance and intestinal microbiome in growing pigs
Authors: Gong Tianye , Ji Mengting , Yang Yuting , Liu Jingchao , Gong Yuxuan , Liu Sijun , Zhao Yan , Cao Guoqing , Guo Xiaohong , Yang Yang , Li Bugao 
Published: December 2024

BackgroundThe use of enzymes within pig feed can reduce the challenges associated with antibiotic-free animal feeding. However, this enzymatic effect is often limited by the internal and external gut environment. This study aimed to improve diet quality and assess the impact of an enzymatically hydrolyzed diet (EHD) on growth performance, meat quality, and intestinal health in growing pigs.MethodsThe EHD was prepared by treating a liquid basal diet with a compound enzyme preparation (5 non-starch polysaccharides (NSP) enzymes: cellulase, pectinase, xylanase, β- glucanase, α-galactosidase; 3 exogenous digestive enzymes: amylase, lipase, protease; lysozyme, and glucose oxidase) in a 1:2.5 ratio with water and heated at 40°C for 1 h. Thirty-six growing pigs (average body weight 25 ± 0.5 kg; age 75 ± 3 days) from the Duroc × Landrace × Yorkshire crossbreed were randomly divided into three dietary groups: solid basal diet (S-CON), liquid basal diet (L-CON), and EHD.ResultsEnzymatic pre-treatment reduced the anti-nutritional factors (ANFs) in the diets (p &lt; 0.01). Additionally, the gluconic acid in the EHD might reduce the pH of diets and inhibit pathogenic bacteria growth. Pigs fed the EHD had higher average daily gains (p &lt; 0.01) and lower feed-to-gain ratios (p &lt; 0.01). Muscle samples revealed higher meat redness and reductions in drip loss, shear force, cooking loss, and meat yellowness (p &lt; 0.01). Moreover, the EHD increased intestinal concentrations of amylase and cellulase (p &lt; 0.01). In terms of gut health, pigs on the EHD diet presented more aligned small intestinal villi, with improved villus height and villus crypt ratio (p &lt; 0.01). There was also up-regulation of the abundance of the tight junction proteins Occludin and ZO-1 and down-regulation of the mRNA expression of TNF-α and IL-6 in the colon (p &lt; 0.05). Additionally, the abundance of beneficial intestinal flora, particularly Firmicutes and Lactobacillus, increased significantly. Lactobacillus and Prevotella were positively correlated with increased short-chain fatty acids.ConclusionOverall, the EHD substantially improved growth performance and intestinal health in pigs, providing a potential reference for improving the effectiveness of enzymatic pretreatment in animal diets.
Relevance of diet in schizophrenia: a review focusing on prenatal nutritional deficiency, obesity, oxidative stress and inflammation
Authors: Rarinca Viorica , Vasile Amalia , Visternicu Malina , Burlui Vasile , Halitchi Gabriela , Ciobica Alin , Singeap Ana-Maria , Dobrin Romeo , Burlui Ecaterina , Maftei Lucian , Trifan Anca 
Published: December 2024

Background/ObjectivesSchizophrenia is a complex mental disorder influenced by genetic and environmental factors, including dietary habits. Oxidative stress and inflammation play a crucial role in the pathophysiology of schizophrenia. Emerging research suggests that diet may affect schizophrenia through different biological mechanisms beyond oxidative stress and inflammation. In particular, epigenetic changes may alter the expression of genes related to neurodevelopment and neurotransmitter systems, while neuroplasticity plays a crucial role in brain adaptation and resilience to psychiatric disorders.MethodsThe literature search included the main available databases (Science Direct, PubMed and Google Scholar), considering the English language, and our screening was performed based on several words such as “schizophrenia”, “diet”, “nutrients”, “obesity”, “oxidative stress”, “inflammation”, “antioxidants” and “prenatal nutritional deficiency”. The review focused specifically on studies examining the relevance of diet in schizophrenia, as well as prenatal nutritional deficiency, obesity, oxidative stress, and inflammation associated with this disorder.ResultsFollowing a review of the literature, it was found that nutritional deficiencies, including lack of omega-3 fatty acids, vitamins D, and B, during the prenatal and postnatal periods can have a negative impact on neurodevelopment and increase the risk of schizophrenia. Patients with schizophrenia have imbalances in antioxidant enzymes, such as glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and reduced levels of antioxidants (vitamin E, vitamin C). These biochemical changes lead to an increase in markers of oxidative stress, including malondialdehyde (MDA). In addition, cytokine-mediated inflammation, microglial activation, and intestinal dysbiosis are associated with the onset of schizophrenia and the severity of schizophrenia symptoms. Currently, there is no universally accepted dietary regimen for control. However, various diets and nutritional methods are being researched and applied to alleviate the symptoms of schizophrenia and improve the overall health of patients, including the Mediterranean diet, the ketogenic diet, the gluten-free diet, and the DASH (Dietary Approaches to Stop Hypertension) diet.ConclusionA healthy diet, rich in anti-inflammatory nutrients and antioxidants, may help manage schizophrenia by reducing oxidative stress, preventing complications, and improving quality of life. Omega-3 fatty acids, vitamin D, and B vitamins are particularly important for brain development and function. In this review, we aim to analyze the literature on the influence of diet on schizophrenia, focusing on the role of prenatal nutritional deficiencies, obesity, oxidative stress, and inflammation.
Predicting epidermal growth factor receptor mutation status of lung adenocarcinoma based on PET/CT images using deep learning
Authors: Huang Lele , Kong Weifang , Luo Yongjun , Xie Hongjun , Liu Jiangyan , Zhang Xin , Zhang Guojin 
Published: December 2024

BackgroundThe aim of this study is to develop deep learning models based on 18F-fluorodeoxyglucose positron emission tomography/computed tomographic (18F-FDG PET/CT) images for predicting individual epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma (LUAD).MethodsWe enrolled 430 patients with non–small-cell lung cancer from two institutions in this study. The advanced Inception V3 model to predict EGFR mutations based on PET/CT images and developed CT, PET, and PET + CT models was used. Additionally, each patient’s clinical characteristics (age, sex, and smoking history) and 18 CT features were recorded and analyzed. Univariate and multivariate regression analyses identified the independent risk factors for EGFR mutations, and a clinical model was established. The performance using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, recall, and F1-value was evaluated. The DeLong test was used to compare the predictive performance across various models.ResultsAmong these four models, deep learning models based on CT and PET + CT exhibit the same predictive performance, followed by PET and the clinical model. The AUC values for CT, PET, PET + CT, and clinical models in the training set are 0.933 (95% CI, 0.922–0.943), 0.895 (95% CI, 0.882–0.907), 0.931 (95% CI, 0.921–0.942), and 0.740 (95% CI, 0.685–0.796), respectively; whereas those in the testing set are:0.921 (95% CI, 0.904–0.938), 0.876 (95% CI, 0.855–0.897), 0.921 (95% CI, 0.904–0.937), and 0.721 (95% CI, 0.629–0.814), respectively. The DeLong test results confirm that all deep learning models are superior to clinical one.ConclusionThe PET/CT images based on trained CNNs effectively predict EGFR and non-EGFR mutations in LUAD. The deep learning predictive models could guide treatment options.
Anesthetic spindles serve as EEG markers of the depth variations in anesthesia induced by multifarious general anesthetics in mouse experiments
Authors: You Ying , Liu Hui , Yang Zhanfei , Chen Yuxuan , Yang Fei , Yu Tian , Zhang Yu 
Published: December 2024

BackgroundMice play a crucial role in studying the mechanisms of general anesthesia. However, identifying reliable EEG markers for different depths of anesthesia induced by multifarious agents remains a significant challenge. Spindle activity, typically observed during NREM sleep, reflects synchronized thalamocortical activity and is characterized by a frequency range of 7–15 Hz and a duration of 0.5–3 s. Similar patterns, referred to as “anesthetic spindles,” are also observed in the EEG during general anesthesia. However, the variability of anesthetic spindles across different anesthetic agents and depths is not yet fully understood.MethodMice were anesthetized with dexmedetomidine, propofol, ketamine, etomidate, isoflurane, or sevoflurane, and cortical EEG recordings were obtained. EEG signals were bandpass filtered between 0.1 and 60 Hz and analyzed using a custom MATLAB script for spindle detection. Anesthesia depth was assessed based on Guedel’s modified stages of anesthesia and the presence of burst suppression in the EEG.ResultsCompared to sleep spindles, anesthetic spindles induced by the different agents exhibited higher amplitudes and longer durations. Isoflurane- and sevoflurane-induced spindles varied with the depth of anesthesia. Spindles associated with etomidate were prominent during induction and light anesthesia, whereas those induced by sevoflurane and isoflurane were more dominant during deep anesthesia and emergence. Post-anesthesia, spindles persisted but ceased more quickly following inhalational anesthesia.ConclusionAnesthesia spindle waves reflect distinct changes in anesthesia depth and persist following emergence, serving as objective EEG markers for assessing both anesthesia depth and the recovery process.
Drug-induced retinal vein occlusion: a disproportionality analysis from the FDA adverse event reporting system (2004–2023)
Authors: Chen Xiao-Dong , Xiao Kun-Hong , Zhou Chao-Bing 
Published: December 2024

IntroductionRetinal vein occlusion (RVO) often causes irreversible visual impairment, making early prevention crucial. This study aims to identify associations between different medications and RVO and provide information for clinical practice.MethodThis study included reports of RVO from the FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2023. The reported drugs were analyzed for adverse drug reaction (ADR) signals using four disproportionality algorithms. Kaplan-Meier curves and median time to onset were used to evaluate the drugs.ResultsFrom 2004 to 2023, the FAERS database recorded 6,151 reports associated with RVO. Disproportionality analyses identified 25 drugs significantly associated with RVO. Mirabegron showed the highest risk signal, followed by Raloxifene, Tadalafil, Fingolimod, and Bimatoprost. These high-risk drugs are distributed across different therapeutic areas, including urogenital system and sex hormones, ophthalmic drugs, nervous system drugs, musculoskeletal system drugs, anti-tumor and immune-modulating drugs, and anti-parasitic drugs. Specific drug targets such as adrenergic receptor agonists, hormone regulators, and PDE5 inhibitors were identified as high risk. Ophthalmic drugs exhibited the longest median time to adverse ocular reactions at 532.01 days, followed by anti-parasitic drugs, nervous system drugs, urogenital system and sex hormone drugs, anti-tumor and immune-modulating drugs, and musculoskeletal system drugs.ConclusionThis study provides an overview of drug-induced RVO, identifying potential culprit drugs and their distribution characteristics. These findings enhance understanding of medication safety and help optimize clinical practice.
Alhagi maurorum extract in combination with lytic phage cocktails: a promising therapeutic approach against biofilms of multi-drug resistant P. mirabilis
Authors: Mirzaei Arezoo , Esfahani Bahram Nasr , Ghanadian Mustafa , Wagemans Jeroen , Lavigne Rob , Moghim Sharareh 
Published: December 2024

Antimicrobial resistance (AMR) poses a significant global threat to public health systems, rendering antibiotics ineffective in treating infectious diseases. Combined use of bio compounds, including bacteriophages and plant extracts, is an attractive approach to controlling antibiotic resistance. In this study, the combination of phage cocktail (Isf-Pm1 and Isf-Pm2) and Alhagi maurorum crude extract (AME) was investigated in controlling biofilm-forming multi-drug resistant P. mirabilis isolates, in vitro and a phantom bladder model. The combination of AME and phage cocktails demonstrated no significant disparity in its ability to inhibit quorum sensing (QS) when compared to the individual control of AME alone. Following treatment with the combination of phage cocktail and AME at a 125 μg/mL concentration, the MDR P. mirabilis biofilm biomass was notably reduced by 73% compared to the control (P&lt; 0.0001). The anti-biofilm effect was confirmed by Scanning Electron Microscopy (SEM). Moreover, in a bladder phantom model, there was a considerable decrease in encrustation levels compared to the control. The combined treatment resulted in a 1.85 logarithmic reduction in bacterial adhesion to Vero cells compared to the control. The real-time PCR results indicated significant downregulation of QS- and adhesion-related gens. The phage therapy, combined with AME, holds promising potential in reducing biofilm formation.
Comparative analysis of mineralocorticoid receptor antagonists and renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitor in heart failure with mildly reduced ejection fraction
Authors: Lee Chia-Chen , Te-Wei Kuan David , Chang Kai-Chun , Chen Zheng-Wei , Cheng Jen-Fang , Lin Ting-Tse , Lin Lian-Yu , Wu Cho-Kai 
Published: December 2024

IntroductionTo clarify the efficacy of mineralocorticoid receptor antagonists (MRA) and renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) in heart failure with mildly reduced ejection fraction (HFmrEF).MethodsThis study assessed the association between these medications and outcomes in HFmrEF using data from the National Taiwan University Hospital-integrated Medical Database. The primary outcome was cardiovascular mortality/heart failure hospitalization (HHF). Inverse probability of treatment weighting balanced baseline patient characteristics. The exposure of primary interest was use of MRA and use of RASI/ARNI, while the non-user group was also likely to receive other heart failure medication treatment.ResultsAmong 2,584 HFmrEF patients, 17% received MRA and 43% received RASI/ARNI. Predictors of MRA use included older age, slightly higher ejection fraction, and lower NT-proBNP level. RASI/ARNI use was predicted by higher BMI, lower NT-proBNP level, normal uric acid and potassium levels. MRA use was not associated with a lower risk of cardiovascular death [hazard ratio = 0.89, 95% confidence interval (CI): 0.78–1.02] or HHF (hazard ratio = 1.01, 95% CI: 0.94–1.09). Conversely, RASI//ARNI use was linked to a lower risk of cardiovascular death (hazard ratio = 0.82, 95% CI: 0.71–0.94) but not HHF (hazard ratio = 0.995, 95% CI: 0.924–1.07). Landmark analysis showed no significant difference in outcomes for follow-up durations exceeding 2 years.ConclusionMRA had a neutral effect on cardiovascular death and HHF, while RASI/ARNI was associated with a lower risk of cardiovascular death. RASI/ARNI may be more beneficial than MRA for HFmrEF patients. Regular re-evaluation is essential to adjust heart failure treatment.
Analysis of genetic instability induced by radon exposure in iron mine processing workers in Shandong Province, Northern China
Authors: Fang Lianying , Wu Fangfang , Sun Hao , Li Weiguo , Hou Dianjun , Ma Ya 
Published: December 2024

BackgroundRadon, a colorless and odorless radioactive gas, poses serious health risks. It is the second leading cause of lung cancer and notably increases lung cancer risk in smokers. Although previous epidemiological studies have mainly examined lung cancer rates in miners, the effects of radon on genomic stability and its molecular mechanisms are not well understood.MethodsThis study evaluated chromosomal aberrations (CA) and cytokinesis-block micronucleus (CBMN) in miners’ lymphocytes, investigating the relationship between cytogenetic damage and variables such as exposure duration and age. Additionally, gene expression profiles were compared between radon-exposed miners and a control group to identify genes involved in DNA damage repair.ResultsWe observed a significant increase in CA and CBMN among underground miners. Gene expression analysis showed 14 genes were upregulated and four downregulated in the exposed group compared to controls.ConclusionThese findings indicate a strong link between high radon exposure and genomic instability in miners. Improved monitoring of work environments and stronger protective measures are critical to safeguarding miners’ health.