bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter hyperintensities in cholinergic pathways are associated with dementia severity in e4 carriers but not in non-carriers
Authors: Yu Ming-Chun , Chuang Yi-Fang , Wu Shu-Ching , Ho Cheng-Feng , Liu Yi-Chien , Chou Chia-Ju 
Published: February 2023

Background and objectivesAmong individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways.MethodsFrom 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating—Sum of Boxes (CDR-SB).ResultsAfter adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group.ConclusionsCarriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.
Dose and time-dependence of acute intermittent theta-burst stimulation on hippocampus-dependent memory in parkinsonian rats
Authors: Wang Yixuan , Liu Jian , Hui Yanping , Wu Zhongheng , Wang Ling , Wu Xiang , Bai Yihua , Zhang Qiaojun , Li Libo 
Published: February 2023

BackgroundThe treatment options for cognitive impairments in Parkinson’s disease (PD) are limited. Repetitive transcranial magnetic stimulation has been applied in various neurological diseases. However, the effect of intermittent theta-burst stimulation (iTBS) as a more developed repetitive transcranial magnetic stimulation paradigm on cognitive dysfunction in PD remains largely unclear.ObjectiveOur aim was to explore the effect of acute iTBS on hippocampus-dependent memory in PD and the mechanism underlying it.MethodsDifferent blocks of iTBS protocols were applied to unilateral 6-hydroxidopamine-induced parkinsonian rats followed by the behavioral, electrophysiological and immunohistochemical analyses. The object-place recognition and hole-board test were used to assess hippocampus-dependent memory.ResultsSham-iTBS and 1 block-iTBS (300 stimuli) didn’t alter hippocampus-dependent memory, hippocampal theta rhythm and the density of c-Fos- and parvalbumin-positive neurons in the hippocampus and medial septum. 3 block-iTBS (900 stimuli) alleviated 6-hydroxidopamine-induced memory impairments, and increased the density of hippocampal c-Fos-positive neurons at 80 min post-stimulation but not 30 min compared to sham-iTBS. Interestingly, 3 block-iTBS first decreased and then increased normalized theta power during a period of 2 h following stimulation. Moreover, 3 block-iTBS decreased the density of parvalbumin-positive neurons in the medial septum at 30 min post-stimulation compared to sham-iTBS.ConclusionThe results indicate that multiple blocks of iTBS elicit dose and time-dependent effects on hippocampus-dependent memory in PD, which may be attributed to changes in c-Fos expression and the power of theta rhythm in the hippocampus.
Functional foods and dietary supplements in the management of non-alcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Wang Lei-lei , Zhang Pian-hong , Yan Hui-hui 
Published: February 2023

ObjectiveIn this systematic review and meta-analysis, we aimed to clarify the overall effects of functional foods and dietary supplements in non-alcoholic fatty liver disease (NAFLD) patients.MethodsRandomized controlled trials (RCTs) published in PubMed, ISI Web of Science, Cochrane library, and Embase from January 1, 2000 to January 31, 2022 were systematically searched to assess the effects of functional foods and dietary supplements in patients with NAFLD. The primary outcomes were liver-related measures, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic fibrosis and steatosis, while the secondary outcomes included body mass index (BMI), waist circumference (WC), triacylglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). These indexes were all continuous variables, so the mean difference (MD) was used for calculating the effect size. Random-effects or fixed-effects models were used to estimate the mean difference (MD). The risk of bias in all studies was assessed with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions.ResultsTwenty-nine articles investigating functional foods and dietary supplements [antioxidants (phytonutrients and coenzyme Q10) = 18, probiotics/symbiotic/prebiotic = 6, fatty acids = 3, vitamin D = 1, and whole grain = 1] met the eligibility criteria. Our results showed that antioxidants could significantly reduce WC (MD: −1.28 cm; 95% CI: −1.58, −0.99, P &lt; 0.05), ALT (MD: −7.65 IU/L; 95% CI: −11.14, −4.16, P &lt; 0.001), AST (MD: −4.26 IU/L; 95% CI: −5.76, −2.76, P &lt; 0.001), and LDL-C (MD: −0.24 mg/dL; 95% CI: −0.46, −0.02, P &lt; 0.05) increased in patients with NAFLD but had no effect on BMI, TG, and TC. Probiotic/symbiotic/prebiotic supplementation could decrease BMI (MD: −0.57 kg/m2; 95% CI: −0.72, −0.42, P &lt; 0.05), ALT (MD: −3.96 IU/L; 95% CI: −5.24, −2.69, P &lt; 0.001), and AST (MD: −2.76; 95% CI: −3.97, −1.56, P &lt; 0.0001) levels but did not have beneficial effects on serum lipid levels compared to the control group. Moreover, the efficacy of fatty acids for treating NAFLD was full of discrepancies. Additionally, vitamin D had no significant effect on BMI, liver transaminase, and serum lipids, while whole grain could reduce ALT and AST but did not affect serum lipid levels.ConclusionThe current study suggests that antioxidant and probiotic/symbiotic/prebiotic supplements may be a promising regimen for NAFLD patients. However, the usage of fatty acids, vitamin D, and whole grain in clinical treatment is uncertain. Further exploration of the efficacy ranks of functional foods and dietary supplements is needed to provide a reliable basis for clinical application.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier: CRD42022351763.
Network pharmacology-based analysis of Resinacein S against non-alcoholic fatty liver disease by modulating lipid metabolism
Authors: Mao Fei-Fei , Gao Shan-Shan , Huang Yan-Jie , Zhou Nian , Feng Jin-Kai , Liu Zong-Han , Zhang Yu-Qing , Yuan Lu-Yun , Wei Gang , Cheng Shu-Qun 
Published: February 2023

BackgroundGanoderma lucidum is reportedly the best source of traditional natural bioactive constituents. Ganoderma triterpenoids (GTs) have been verified as an alternative adjuvant for treating leukemia, cancer, hepatitis and diabetes. One of the major triterpenoids, Resinacein S, has been found to regulate lipid metabolism and mitochondrial biogenesis. Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that has become a major public health problem. Given the regulatory effects on lipid metabolism of Resinacein S, we sought to explore potential protective effects against NAFLD.MethodsResinacein S was extracted and isolated from G. lucidum. And mice were fed with high fat diet with or without Resinacein S to detect hepatic steatosis. According to Network Pharmacology and RNA-seq, we analyzed the hub genes of Resinacein S against NAFLD disease.ResultsOur results can be summarized as follows: (1) The structure of Resinacein S was elucidated using NMR and MS methods. (2) Resinacein S treatment could significantly attenuate high-fat diet (HFD)-induced hepatic steatosis and hepatic lipid accumulation in mouse. (3) GO terms, KEGG pathways and the PPI network of Resinacein S induced Differentially Expressed Genes (DEGs) demonstrated the key target genes of Resinacein S against NAFLD. (4) The hub proteins in PPI network analysis could be used for NAFLD diagnosis and treatment as drug targets.ConclusionResinacein S can significantly change the lipid metabolism in liver cells and yield a protective effect against steatosis and liver injury. Intersected proteins between NAFLD related genes and Resinacein S-induced DEGs, especially the hub protein in PPI network analysis, can be used to characterize targets of Resinacein S against NAFLD.
Comprehensive genomic profiling: Does timing matter?
Authors: Thapa Bicky , Ahmed Gulrayz , Szabo Aniko , Kamgar Mandana , Kilari Deepak , Mehdi Maahum , Menon Smitha , Daniel Sherin , Thompson Jonathan , Thomas James , George Ben 
Published: February 2023

PurposeThere is variability in utilization of Comprehensive Genomic Profiling (CGP) in most of the metastatic solid tumors (MST). We evaluated the CGP utilization patterns and its impact on outcomes at an academic tertiary center.Patients and MethodsInstitutional database was reviewed for CGP data in adult patients with MST between 01/2012 – 04/2020. Patients were categorized based on interval between CGP and metastatic diagnosis; 3 tertiles of distribution (T1-earliest to the diagnosis, T3-furthest), and pre-mets (CGP performed prior to diagnosis of metastasis). Overall survival (OS) was estimated from the time of metastatic diagnosis with left truncation at the time of CGP. Cox regression model was used to estimate the impact of timing of CGP on survival.ResultsAmong 1,358 patients, 710 were female, 1,109 Caucasian, 186 Afro-Americans, and 36 Hispanic. The common histologies were lung cancer (254; 19%), colorectal cancer (203; 15%), gynecologic cancers (121; 8.9%), and pancreatic cancer (106; 7.8%). Time interval between diagnosis of metastatic disease and CGP was not statistically significantly different based on sex, race and ethnicity after adjusting for histologic diagnoses with 2 exceptions - Hispanics with lung cancer had delayed CGP compared to non-Hispanics (p =0.019) and females with pancreas cancer had delayed CGP compared to males (p =0.025). Lung cancer, gastro-esophageal cancer and gynecologic malignancies had better survival if they had CGP performed during the first tertile after metastatic diagnosis.ConclusionCGP utilization across cancer types was equitable irrespective of sex, race and ethnicity. Early CGP after metastatic diagnosis might have effect on treatment delivery and clinical outcomes in cancer type with more actionable targets.
Integrated multi-dimensional deep neural network model improves prognosis prediction of advanced NSCLC patients receiving bevacizumab
Authors: Li Butuo , Yang Linlin , Jiang Chao , Yao Yueyuan , Li Haoqian , Cheng Shuping , Zou Bing , Fan Bingjie , Wang Linlin 
Published: February 2023

BackgroundThe addition of bevacizumab was found to be associated with prolonged survival whether in combination with chemotherapy, tyrosine kinase inhibitors or immune checkpoint inhibitors in the treatment landscape of advanced non-small cell lung cancer (NSCLC) patients. However, the biomarkers for efficacy of bevacizumab were still largely unknown. This study aimed to develop a deep learning model to provide individual assessment of survival in advanced NSCLC patients receiving bevacizumab.MethodsAll data were retrospectively collected from a cohort of 272 radiological and pathological proven advanced non-squamous NSCLC patients. A novel multi-dimensional deep neural network (DNN) models were trained based on clinicopathological, inflammatory and radiomics features using DeepSurv and N-MTLR algorithm. And concordance index (C-index) and bier score was used to demonstrate the discriminatory and predictive capacity of the model.ResultsThe integration of clinicopathologic, inflammatory and radiomics features representation was performed using DeepSurv and N-MTLR with the C-index of 0.712 and 0.701 in testing cohort. And Cox proportional hazard (CPH) and random survival forest (RSF) models were also developed after data pre-processing and feature selection with the C-index of 0.665 and 0.679 respectively. DeepSurv prognostic model, indicated with best performance, was used for individual prognosis prediction. And patients divided in high-risk group were significantly associated with inferior PFS (median PFS: 5.4 vs 13.1 months, P&lt;0.0001) and OS (median OS: 16.4 vs 21.3 months, P&lt;0.0001).ConclusionsThe integration of clinicopathologic, inflammatory and radiomics features representation based on DeepSurv model exhibited superior predictive accuracy as non-invasive method to assist in patients counseling and guidance of optimal treatment strategies.
Impact of the COVID-19 pandemic on the digitization of routine pediatric practice in Spain: A nationwide survey study
Authors: Martín-Masot Rafael , Diaz-Martin Juan J. , Santamaría-Orleans Alicia , Navas-López Víctor Manuel 
Published: February 2023

IntroductionThe COVID-19 pandemic forced a change in the working dynamics of all healthcare professionals, leading to the sudden introduction of telemedicine. Although until that moment telemedicine applications had been described in the paediatric age, their use was anecdotal.ObjectiveTo analyse the experience of Spanish paediatricians after the forced digitization of consultations due to the pandemic.MethodsA cross-sectional survey-type study was designed to obtain information from Spanish paediatricians about the changes that took place in the usual clinical practice.Results306 health professionals participated in the study Most of them agreed on the use of the internet and social networks during the pandemic, referring to mail or WhatsApp® as usual channels of communication with their patients' families. There was a great agreement among paediatricians that the evaluation of newborns after hospital discharge and establishing methodologies that allow childhood vaccination and the identification of subsidiary patients for face-to-face evaluation were necessary although the limitations of the lockdown. The idea that telephone and digital consultations have optimized the consultation time and that they will probably continue after the end of the pandemic was generally accepted. No changes in adherence to breastfeeding or the start of complementary feeding were referred to, but an increase in the duration of breastfeeding and the appearance of frequent hoaxes in social networks concerning infant feeding were found.ConclusionsIt is necessary to analyse the impact of telemedicine in paediatric consultations during the pandemic to evaluate its effectiveness and quality to maintain it in routine paediatric practice.
Intraoperative monitoring of cerebrovascular autoregulation in infants and toddlers receiving major elective surgery to determine the individually optimal blood pressure – a pilot study
Authors: Iller Maximilian , Neunhoeffer Felix , Heimann Lukas , Zipfel Julian , Schuhmann Martin U. , Scherer Simon , Dietzel Markus , Fuchs Joerg , Hofbeck Michael , Hieber Stefanie , Fideler Frank 
Published: February 2023

IntroductionInducing general anesthesia (GA) in children can considerably affect blood pressure, and the rate of severe critical events owing to this remains high. Cerebrovascular autoregulation (CAR) protects the brain against blood-flow-related injury. Impaired CAR may contribute to the risk of cerebral hypoxic–ischemic or hyperemic injury. However, blood pressure limits of autoregulation (LAR) in infants and children are unclear.Materials and methodsIn this pilot study CAR was monitored prospectively in 20 patients aged &lt;4 years receiving elective surgery under GA. Cardiac- or neurosurgical procedures were excluded. The possibility of calculating the CAR index hemoglobin volume index (HVx), by correlating near-infrared-spectroscopy (NIRS)-derived relative cerebral tissue hemoglobin and invasive mean arterial blood pressure (MAP) was determined. Optimal MAP (MAPopt), LAR, and the proportion of time with a MAP outside LAR were determined.ResultsThe mean patient age was 14 ± 10 months. MAPopt could be determined in 19 of 20 patients, with an average of 62 ± 12 mmHg. The required time for a first MAPopt depended on the extent of spontaneous MAP fluctuations. The actual MAP was outside the LAR in 30% ± 24% of the measuring time. MAPopt significantly differed among patients with similar demographics. The CAR range averaged 19 ± 6 mmHg. Using weight-adjusted blood pressure recommendations or regional cerebral tissue saturation, only a fraction of the phases with inadequate MAP could be identified.ConclusionNon-invasive CAR monitoring using NIRS-derived HVx in infants, toddlers, and children receiving elective surgery under GA was reliable and provided robust data in this pilot study. Using a CAR-driven approach, individual MAPopt could be determined intraoperatively. The intensity of blood pressure fluctuations influences the initial measuring time. MAPopt may differ considerably from recommendations in the literature, and the MAP range within LAR in children may be smaller than that in adults. The necessity of manual artifact elimination represents a limitation. Larger prospective and multicenter cohort studies are necessary to confirm the feasibility of CAR-driven MAP management in children receiving major surgery under GA and to enable an interventional trial design using MAPopt as a target.
A comprehensive overview of clinical research on dexmedetomidine in the past 2 decades: A bibliometric analysis
Authors: Kong Hao , Li Mo , Deng Chun-Mei , Wu Yu-Jia , He Shu-Ting , Mu Dong-Liang 
Published: February 2023

Introduction: Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist with sedative, analgesic, anxiolytic, and opioid-sparing properties. A large number of dexmedetomidine-related publications have sprung out in the last 2 decades. However, no bibliometric analysis for clinical research on dexmedetomidine has been published to analyze hot spots, trends, and frontiers in this field.Methods: The clinical articles and reviews related to dexmedetomidine, published from 2002 to 2021 in the Web of Science Core Collection, were retrieved on 19 May 2022, using relevant search terms. VOSviewer and CiteSpace were used to conduct this bibliometric study.Results: The results showed that a total of 2,299 publications were retrieved from 656 academic journals with 48,549 co-cited references by 2,335 institutions from 65 countries/regions. The United States had the most publications among all the countries (n = 870, 37.8%) and the Harvard University contributed the most among all institutions (n = 57, 2.48%). The most productive academic journal on dexmedetomidine was Pediatric Anesthesia and the first co-cited journal was Anesthesiology. Mika Scheinin is the most productive author and Pratik P Pandharipande is the most co-cited author. Co-cited reference analysis and keyword analysis illustrated hot spots in the dexmedetomidine field including pharmacokinetics and pharmacodynamics, intensive care unit sedation and outcome, pain management and nerve block, and premedication and use in children. The effect of dexmedetomidine sedation on the outcomes of critically ill patients, the analgesic effect of dexmedetomidine, and its organ protective property are the frontiers in future research.Conclusion: This bibliometric analysis provided us with concise information about the development trend and provided an important reference for researchers to guide future research.
Systematic investigation of the underlying mechanisms of GLP-1 receptor agonists to prevent myocardial infarction in patients with type 2 diabetes mellitus using network pharmacology
Authors: Deng Guorong , Ren Jiajia , Li Ruohan , Li Minjie , Jin Xuting , Li Jiamei , Liu Jueheng , Gao Ya , Zhang Jingjing , Wang Xiaochuang , Wang Gang 
Published: February 2023

Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM.Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules.Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications.Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis.