bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of diagnostic accuracy for diabetes diagnosis: A systematic review and network meta-analysis
Authors: Duong Khanh N. C. , Tan Chia Jie , Rattanasiri Sasivimol , Thakkinstian Ammarin , Anothaisintawee Thunyarat , Chaiyakunapruk Nathorn 
Published: January 2023

AimFasting Plasma Glucose (FPG) and Hemoglobin A1c (HbA1c) are used as diagnostic tests for diagnosing diabetes mellitus, but it is unclear which test has the best diagnostic accuracy. This systematic review and network meta-analysis aimed to estimate the diagnostic accuracy of HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and the combination of HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl (HbA1c| FPG), compared with Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dl for diagnosis diabetes.Materials and methodsWe performed a comprehensive search in PubMed, Embase, Cochrane Library, and Scopus from inception to September 24th, 2021. Inclusion criteria were any study design comparing HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl with OGTT ≥ 200 mg/dl as the reference test. Data were independently extracted, risk of bias was assessed using QUADAS-2 by two reviewers. Network meta-analysis was done using a bivariate regression model using the Bayesian framework. The relative ranking of all tests was also assessed.ResultsOut of 5,026 studies, 73 were included. The sensitivities of HbA1c, FPG, and HbA1c| FPG were 0.51 [95% Credible Interval (CrI): 0.43, 0.58], 0.49 (95% CrI: 0.43, 0.55), and 0.64 (95% CrI: 0.51, 0.75), while the specificities were 0.96 (95% CrI: 0.94, 0.97), 0.98 (95% CrI: 0.97, 0.98), and 0.95 (95% CrI: 0.88, 0.98), respectively. The corresponding positive likelihood ratios (LR) were 13.36 (95% CrI: 8.91, 20.72), 21.94 (95% CrI: 15.04, 31.88), and 11.78 (95% CrI: 5.48, 26.56). HbA1c| FPG is superior based on sensitivity, whereas FPG is ranked best based on specificity and positive LR.ConclusionOur findings suggest that FPG ≥ 126 mg/dl should be recommended as the best diagnostic test for diabetes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021282856.
Effects of electroacupuncture on urinary metabolome and microbiota in presenilin1/2 conditional double knockout mice
Authors: Gao Jie , Zhou Nian , Lu Mengna , Wang Qixue , Zhao Chenyi , Wang Jian , Zhou Mingmei , Xu Ying 
Published: January 2023

AimThe treatment of Alzheimer’s disease (AD) is still a worldwide problem due to the unclear pathogenesis and lack of effective therapeutic targets. In recent years, metabolomic and gut microbiome changes in patients with AD have received increasing attention, and the microbiome–gut–brain (MGB) axis has been proposed as a new hypothesis for its etiology. Considering that electroacupuncture (EA) efficiently moderates cognitive deficits in AD and its mechanisms remain poorly understood, especially regarding its effects on the gut microbiota, we performed urinary metabolomic and microbial community profiling on EA-treated AD model mice, presenilin 1/2 conditional double knockout (PS cDKO) mice, to observe the effect of EA treatment on the gut microbiota in AD and find the connection between affected gut microbiota and metabolites.Materials and methodsAfter 30 days of EA treatment, the recognition memory ability of PS cDKO mice was evaluated by the Y maze and the novel object recognition task. Urinary metabolomic profiling was conducted with the untargeted GC-MS method, and 16S rRNA sequence analysis was applied to analyze the microbial community. In addition, the association between differential urinary metabolites and gut microbiota was clarified by Spearman’s correlation coefficient analysis.Key findingsIn addition to reversed cognitive deficits, the urinary metabolome and gut microbiota of PS cDKO mice were altered as a result of EA treatment. Notably, the increased level of isovalerylglycine and the decreased levels of glycine and threonic acid in the urine of PS cDKO mice were reversed by EA treatment, which is involved in glyoxylate and dicarboxylate metabolism, as well as glycine, serine, and threonine metabolism. In addition to significantly enhancing the diversity and richness of the microbial community, EA treatment significantly increased the abundance of the genus Mucispirillum, while displaying no remarkable effect on the other major altered gut microbiota in PS cDKO mice, norank_f_Muribaculaceae, Lactobacillus, and Lachnospiraceae_NK4A136 group. There was a significant correlation between differential urinary metabolites and differential gut microbiota.SignificanceElectroacupuncture alleviates cognitive deficits in AD by modulating gut microbiota and metabolites. Mucispirillum might play an important role in the underlying mechanism of EA treatment. Our study provides a reference for future treatment of AD from the MGB axis.
Quinate-based ligands for irreversible inactivation of the bacterial virulence factor DHQ1 enzyme—A molecular insight†
Authors: Rodríguez Ángela , Maneiro María , Lence Emilio , Otero José M. , van Raaij Mark J. , Thompson Paul , Hawkins Alastair R. , González-Bello Concepción 
Published: January 2023

Irreversible inhibition of the enzyme type I dehydroquinase (DHQ1), a promising target for anti-virulence drug development, has been explored by enhancing the electrophilicity of specific positions of the ligand towards covalent lysine modification. For ligand design, we made use of the advantages offered by the intrinsic acid-base properties of the amino substituents introduced in the quinate scaffold, namely compounds 6–7 (R configuration at C3), to generate a potential leaving group, as well as the recognition pattern of the enzyme. The reactivity of the C2–C3 bond (Re face) in the scaffold was also explored using compound 8. The results of the present study show that replacement of the C3 hydroxy group of (–)-quinic acid by a hydroxyamino substituent (compound 6) provides a time-dependent irreversible inhibitor, while compound 7, in which the latter functionality was substituted by an amino group, and the introduction of an oxirane ring at C2–C3 bond, compound 8, do not allow covalent modification of the enzyme. These outcomes were supported by resolution of the crystal structures of DHQ1 from Staphylococcus aureus (Sa-DHQ1) and Salmonella typhi (St-DHQ1) chemically modified by 6 at a resolution of 1.65 and 1.90 Å, respectively, and of St-DHQ1 in the complex with 8 (1.55 Å). The combination of these structural studies with extensive molecular dynamics simulation studies allowed us to understand the molecular basis of the type of inhibition observed. This study is a good example of the importance of achieving the correct geometry between the reactive center of the ligand (electrophile) and the enzyme nucleophile (lysine residue) to allow selective covalent modification. The outcomes obtained with the hydroxyamino derivative 6 also open up new possibilities in the design of irreversible inhibitors based on the use of amino substituents.
Cerebral blood flow changes induced by high-frequency repetitive transcranial magnetic stimulation combined with cognitive training in Alzheimer's disease
Authors: Qin Yuanyuan , Ba Li , Zhang Fengxia , Jian Si , Zhang Min , Zhu Wenzhen 
Published: January 2023

Background and purposeHypoperfusion of the posterior cingulate cortex (PCC) and precuneus has consistently been reported in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (COG) is effective in alleviating the symptoms of patients with mild AD. This study investigated the effects of rTMS-COG therapy on cerebral blood flow (CBF), with a special interest in the PCC/precuneus, and whether observed CBF changes are associated with changes in neuropsychological assessments in AD.Materials and methodsTwenty-one patients with mild or moderate AD were randomly divided into real rTMS (n = 11) and sham treatment (n = 10) groups, both combined with COG. Neuro-navigated 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex (DLPFC) and then the left lateral temporal lobe (LTL) for 20 min each day for 4 weeks in the real rTMS group. All patients with AD underwent neuropsychological assessment, pseudo-continuous arterial spin labeling, and structural 3D T1-weighted MRI before treatment (T0), immediately after treatment (T1), and 4 weeks after treatment (T2). CBF in the precuneus, PCC, and stimulation targets at the region-of-interest (ROI) level, as well as whole-brain CBF changes at the voxel level, were compared between the two groups at three timepoints.ResultsrTMS-COG therapy revealed significant group × time interactions for the Mini-Mental State Examination (F = 5.339, p = 0.023, η2 = 0.433) and activities of daily living (F = 5.409, p = 0.039, η2 = 0.436) scores. The regional CBF in the precuneus showed a significant group × time interaction (F = 5.833, p = 0.027, η2 = 0.593). For voxel-level analysis, a significant group main effect was found in the left limbic lobe cluster, with the maximal peak in the left parahippocampus (p &lt; 0.001, uncorrected, peak at [−16 −8 −24]). Simple effects analysis indicated that rTMS-COG therapy induced a decrease in CBF in the precuneus at T1 (p = 0.007) and an increase in the left parahippocampus at T2 (p=0.008). CBF decrease in the precuneus was correlated with better cognitive function immediately after treatment (T1) (r =−0.732, p=0.025).ConclusionNeuropsychological assessments showed immediate and long-term effects on cognitive function and activities of daily living after rTMS-COG therapy. CBF changes induced by high-frequency rTMS-COG therapy are region-dependent, showing immediate effects in the precuneus and long-term effects in the left parahippocampus. These results provide imaging evidence to understand the underlying neurobiological mechanism for the application of rTMS-COG in AD.
Using fNIRS to evaluate ADHD medication effects on neuronal activity: A systematic literature review
Authors: Poliakova Eva , Conrad Amy L. , Schieltz Kelly M. , O'Brien Matthew J. 
Published: January 2023

BackgroundFunctional near infrared spectroscopy (fNIRS) is a relatively non-invasive and inexpensive functional neuroimaging technique that has shown promise as a method for understanding the differences in neuronal activity associated with various neurodevelopmental conditions, including ADHD. Additionally, fNIRS has been suggested as a possible tool to understand the impact of psychotropic medications on brain activity in individuals with ADHD, but this approach is still in its infancy.ObjectiveThe purpose of this systematic literature review was to synthesize the extant research literature on the use of fNIRS to assess the effects of ADHD medications on brain activity in children and adolescents with ADHD.MethodsA literature search following Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) guidelines was conducted for peer-reviewed articles related to ADHD, medication, and fNIRS in PsychInfo, Scopus, and PubMed electronic databases.ResultsThe search yielded 23 published studies meeting inclusion criteria. There was a high degree of heterogeneity in terms of the research methodology and procedures, which is explained in part by the distinct goals and approaches of the studies reviewed. However, there was also relative consistency in outcomes among a select group of studies that demonstrated a similar research focus.ConclusionAlthough fNIRS has great potential to further our understanding of the effects of ADHD medications on the neuronal activity of children and adolescents with ADHD, the current research base is still relatively small and there are limitations and methodological inconsistencies that should be addressed in future studies.
Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification
Authors: Zhi Guoguo , Shao Bingjie , Zheng Tianyan , Mu Jie , Li Jingwei , Feng Yiyuan , Zhu Sha , Dang Yanni , Liu Feng , Wang Dong 
Published: January 2023

Background: With the gradual increase in prevalence in recent years, non-alcoholic steatohepatitis (NASH) has become one of the significant health problems that urgently needs to be addressed worldwide. GanShuang Granules (GSG) is derived from the classical Chinese formula Xiaoyao San and mainly used in the clinical treatment of chronic liver diseases.Objective: In this study, we aim to gain a deeper insight into the inhibiting effects of GSG on non-alcoholic fatty liver disease (NAFLD) rats and preliminarily elucidate the underlying intervention mechanisms.Methods: First, High performance liquid chromatography (UHPLC-Q/Orbitrap-MS/MS) was used for the active compounds prediction in GSG. Then the data was mapped to mzCloud database. The targets corresponding to GSG compounds were collected from public databases, along with disease genes for NAFLD. The core targets and molecular mechanisms of GSG for NAFLD treatment were predicted by protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Molecular docking of the core target-component interactions was simulated using AutoDock Vina software. The effect of GSG on NASH rats was evaluated by pathological staining and analysis of various index results. Finally, the candidate targets were further validated by ELISA and western blot (WB) analyses.Results: Combining UHPLC-Q/Orbitrap-MS/MS data analysis and public database data, a total of 346 cross-targets were obtained, corresponding to 81 compounds. The subnetwork with an MCODE score of 53.623 is a potential core target group for this study. GO and KEGG enrichment analyses showed that the targets of GSG in NAFLD were mostly related to oxidative stress, the NF-κB signaling pathway, and the apoptosis signaling pathway. By integrating the results of network pharmacology analysis, the core objectives of this study mainly include AKT1, CASP9, TNF, and CASP8. The core ingredients are related to resveratrol and fisetin. The molecular docking results indicated key binding activity between AKT1-fisetin, AKT1-Resveratrol, and CASP8-fisetin. Moreover, GSG could improve the inflammatory status and restore the abnormal lipid accumulation of NAFLD/NASH liver, and these levels are further verified by pathological staining and detection of related indicators. Mechanistically, GSG could regulate protein expression levels in the liver for P65, p-P65, IKB, p-IKB, IKK, caspase-3, -8, -9, and cytochrome C, etc. It reflects the inhibitory effect of GSG on the NF-κB/IκB signaling pathway.Conclusion: Our results suggested that GSG demonstrated therapeutic effects on NAFLD/NASH rats, and these may be mainly reflected in the inhibitory effects on the NF-κB/IκB signaling pathway and its downstream inflammation and apoptosis signals.
Gene coexpression analysis reveals key pathways and hub genes related to late-acting self-incompatibility in Camellia oleifera
Authors: Li Chang , Long Yi , Lu Mengqi , Zhou Junqin , Wang Sen , Xu Yan , Tan Xiaofeng 
Published: January 2023

IntroductionSelf-incompatibility (SI) is an important strategy for plants to maintain abundant variation to enhance their adaptability to the environment. Camellia oleifera is one of the most important woody oil plants and is widely cultivated in China. Late acting self-incompatibility (LSI) in C. oleifera results in a relatively poor fruit yield in the natural state, and understanding of the LSI mechanism remains limited. MethodsTo better understand the molecular expression and gene coexpression network in the LSI reaction in C. oleifera, we conducted self- and cross-pollination experiments at two different flower bud developmental stages (3–4 d before flowering and 1 d before flowering), and cytological observation, fruit setting rate (FSR) investigation and RNA-Seq analysis were performed to investigate the mechanism of the male −female interaction and identify hub genes responsible for the LSI in C. oleifera.ResultsBased on the 21 ovary transcriptomes, a total of 7669 DEGs were identified after filtering out low-expression genes. Weighted gene coexpression network analysis (WGCNA) divided the DEGs into 15 modules. Genes in the blue module (1163 genes) were positively correlated with FSR, and genes in the pink module (339 genes) were negatively correlated with FSR. KEGG analysis indicated that flavonoid biosynthesis, plant MAPK signaling pathways, ubiquitin-mediated proteolysis, and plant-pathogen interaction were the crucial pathways for the LSI reaction. Fifty four transcription factors (TFs) were obtained in the two key modules, and WRKY and MYB were potentially involved in the LSI reaction in C. oleifera. Network establishment indicated that genes encoding G-type lectin S-receptor-like serine (lecRLK), isoflavone 3’-hydroxylase-like (CYP81Q32), cytochrome P450 87A3-like (CYP87A3), and probable calcium-binding protein (CML41) were the hub genes that positively responded to the LSI reaction. The other DEGs inside the two modules, including protein RALF-like 10 (RALF), F-box and pectin acetylesterase (MTERF5), might also play vital roles in the LSI reaction in C. oleifera.DiscussionOverall, our study provides a meaningful resource for gene network studies of the LSI reaction process and subsequent analyses of pollen−pistil interactions and TF roles in the LSI reaction, and it also provides new insights for exploring the mechanisms of the LSI response.
The necessity revealed by COVID-19 pandemic: Paradigm shift of Iran's healthcare system
Authors: Mohammadpour Mohammadtaghi , Delavari Sajad , Kavosi Zahra , Peyravi Mahmoudreza , Izadi Reyhane , Bastani Peivand 
Published: January 2023

BackgroundCOVID-19 pandemic has resulted in drastic changes around the world, revealing vulnerable aspects of healthcare systems. This study aimed to explore how Iranian healthcare system experienced the paradigm shift during the pandemic and determine the aspects that need improvement during the pandemic era.MethodThis qualitative study was conducted in 2021. A framework analysis approach was used to analyze the content of the 19 semi-structured interviews with the healthcare system experts from Shiraz University of Medical Sciences (SUMS). The interviews‘ audio files changed into transcript after each session and data was saturated at the 19 interview. To increase the trustworthiness of the study, Guba and Lincoln's criteria including credibility, transferability, dependability, and confirmability were used. Goldsmith's five-step framework analysis was used applying MAX QDA version 10 software.ResultEight main themes and 20 subthemes were explored. The main themes included “strengthening the electronic health infrastructure,” “research for evidence-based decision making,” “dedicated financing to the pandemic,” “prevention of disruption in the effective provision of services and medicines,” “enriching the authority of the Ministry of Health by focusing on interactions,” “recruiting, managing and empowering health human resources with attention to financial and non-financial incentives,” “reforming educational approaches in training students in medical universities,” as well as “lessons learned from neglected aspects.”ConclusionTo be ready to respond to a possible future pandemic and for a paradigm shift, bold steps must be taken to make fundamental changes in various aspects of the healthcare system including e-health development, evidence-based decision making, dedicated budgets for pandemics, reinforcement of interactions at the national and international level, as well as sufficient attention to healthcare workers from all financial, non-financial and educational aspects.
Food insecurity and its socioeconomic and health determinants in pregnant women and mothers of children under 2 years of age, during the COVID-19 pandemic: A systematic review and meta-analysis
Authors: Azevedo Francilene Maria , Morais Núbia de Souza de , Silva Debora Leticia Frizzi , Candido Aline Carare , Morais Dayane de Castro , Priore Silvia Eloiza , Franceschini Sylvia do Carmo Castro 
Published: January 2023

BackgroundThe COVID-19 pandemic has reduced access to adequate food in terms of quality and quantity, especially for the most vulnerable population groups. The objective of this study was to evaluate the prevalence of Food Insecurity and its main socioeconomic and health determinants in pregnant women and mothers of children under 2 years of age, during the COVID-19 pandemic.MethodsThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021278033). The descriptors “Pregnant Woman”, “Postpartum Women”, “Breastfeeding Women”, “COVID-19”, “Food Insecurity”, “Food Security” were combined in Scopus (Elsevier), Medline/PubMed (via National Library of Medicine), Embase (Elsevier), Web of Science and Science Direct independently by two researchers in September 2022. Original articles about Food Insecurity in households with pregnant women and mothers of children under 2 years of age during the COVID-19 pandemic were included. The meta-analysis of the prevalence of Food Insecurity was conducted using the RStudio software (4.0.4).ResultsThe initial search resulted in 539 records, and 10 articles met the proposed criteria and were included in this review. The prevalence of Food Insecurity ranged from 11.5 to 80.3% and in the meta-analysis it was 51% (IC: 30–71) (I2 = 100.0%). The main socioeconomic and health determinants were ethnicity, domain language, low education, low income, informal employment, unemployment, occurrence of mental disorders, domestic violence, in addition to the unavailability of food in markets and lack of transport. The inclusion of studies with data collection by telephone stands out as a limitation, due to the non-inclusion of vulnerable groups without access to this means of communication.ConclusionIt is necessary to implement and strengthen specific public policies for the maternal and child group with the objective of protecting and strengthening the rights of women to maintain the physical and mental integrity of this group and guarantee Food Security.