bluuebunny/crossref_metadata_2025_split huggingface dataset:
The construction and analysis of tricarboxylic acid cycle related prognostic model for cervical cancer
Authors: Chen Guanqiao , Hong Xiaoshan , He Wanshan , Ou Lingling , Chen Bin , Zhong Weitao , Lin Yu , Luo Xiping 
Published: March 2023

Introduction: Cervical cancer (CC) is the fourth most common malignant tumor in term of in incidence and mortality among women worldwide. The tricarboxylic acid (TCA) cycle is an important hub of energy metabolism, networking one-carbon metabolism, fatty acyl metabolism and glycolysis. It can be seen that the reprogramming of cell metabolism including TCA cycle plays an indispensable role in tumorigenesis and development. We aimed to identify genes related to the TCA cycle as prognostic markers in CC.Methods: Firstly, we performed the differential expressed analysis the gene expression profiles associated with TCA cycle obtained from The Cancer Genome Atlas (TCGA) database. Differential gene list was generated and cluster analysis was performed using genes with detected fold changes &gt;1.5. Based on the subclusters of CC, we analysed the relationship between different clusters and clinical information. Next, Cox univariate and multivariate regression analysis were used to screen genes with prognostic characteristics, and risk scores were calculated according to the genes with prognostic characteristics. Additionally, we analyzed the correlation between the predictive signature and the treatment response of CC patients. Finally, we detected the expression of ench prognostic gene in clinical CC samples by quantitative polymerase chain reaction (RT-qPCR).Results: We constructed a prognostic model consist of seven TCA cycle associated gene (ACSL1, ALDOA, FOXK2, GPI, MDH1B, MDH2, and MTHFD1). Patients with CC were separated into two groups according to median risk score, and high-risk group had a worse prognosis compared to the low-risk group. High risk group had lower level of sensitivity to the conventional chemotherapy drugs including cisplatin, paclitaxel, sunitinib and docetaxel. The expression of ench prognostic signature in clinical CC samples was verified by qRT-PCR.Conclusion: There are several differentially expressed genes (DEGs) related to TCA cycle in CC. The risk score model based on these genes can effectively predict the prognosis of patients and provide tumor markers for predicting the prognosis of CC.
The causality between intestinal flora and allergic diseases: Insights from a bi-directional two-sample Mendelian randomization analysis
Authors: Jin Qiubai , Ren Feihong , Dai Dan , Sun Nan , Qian Yiyun , Song Ping 
Published: March 2023

BackgroundGrowing evidence shows a significant association between intestinal flora and allergic diseases, specifically atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). However, the causality has not yet been clarified.ObjectiveWe conducted a bidirectional two-sample Mendelian randomization (TSMR) analysis to study the causal relationships between intestinal flora classification and AD, AR, or AA.Materials and methodsWe obtained summary data of intestinal flora, AD, AR, and AA from a genome-wide association research. The inverse-variance weighted method is the primary method for analyzing causality in the TSMR analysis. Several sensitivity analyses were conducted to examine the stability of TSMR results. Reverse TSMR analysis was also performed to assess whether there was a reverse causality.ResultsA total of 7 bacterial taxa associated with AD, AR, and AA were identified by the current TSMR analysis. Specifically, the genus Dialister(P=0.034)and genus Prevotella(P=0.047)were associated with a higher risk of AD, whereas class Coriobacteriia (P=0.034) and its child taxon, order Coriobacteriales (P=0.034) and family Coriobacteriaceae (P=0.034), all had a protective effect on AR. In addition, the family Victivallaceae (P=0.019) was identified as a risk factor for AR. We also noticed a positive association between the genus Holdemanella (P=0.046) and AA. The reverse TSMR analysis didn’t suggest any evidence of reverse causality from allergic diseases to the intestinal flora.ConclusionWe confirmed the causal relationship between intestinal flora and allergic diseases and provided an innovative perspective for research on allergic diseases: targeted regulation of dysregulation of specific bacterial taxa to prevent and treat AD, AR, and AA.
Assessment of marine ecosystem health and its key influencing factors in Laizhou Bay, China
Authors: Wu Wen , Hu Jinming , Song Dehai 
Published: March 2023

IntroductionMajor bays worldwide have been disturbed by human pressures to varying degrees in recent years, resulting in many ecological and environmental issues. Maintaining the health of the bay ecosystem has national and international significances, as it enhances the environmental regulation function and resource development value of the region. This study aims to examine the evolution trend and regulatory mechanism of ecosystem health in Laizhou Bay (LZB), China.MethodsA comprehensive DPSIR-based indicator framework is established, comprising 40 representative indicators of the natural environment status, ecological service function, and social values of the LZB ecosystem. The subjective and objective integrated weighting method is applied to determine the indicator weight. The Ecosystem Health Index is then calculated to assess the LZB ecosystem health from 1980 to 2019 and key influencing factors are identified through the scenario analysis. ResultsThe results show that the health status of the LZB ecosystem has fluctuated and then increased overall over the past 40 years, with a fairly healthy state in the 1980s, an unhealthy state in 2005, and then a rebound to a subhealthy state. The key factors affecting the LZB ecosystem health are mostly pressure items, with land-based pollution, particularly agricultural non-point source pollution, having a more significant impact than reclamations.DiscussionReasonable recommendations are finally put forward on improving the ecosystem health in the study area, including refining the legislation and integrated mechanism related to regional management, building a coordinated land-sea governance system and exploring new technologies for integrated marine management. This study fills the knowledge gap of ecosystem health assessment for the entire LZB in such a long-time scale, and the research outcomes are expected to provide scientific references and guidance for decision-making and social-economic sustainable development in LZB and other bays.
Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis
Authors: Margaroli Camilla , Benson Paul , Gastanadui Maria G. , Song Chunyan , Viera Liliana , Xing Dongqi , Wells J. Michael , Patel Rakesh , Gaggar Amit , Payne Gregory A. 
Published: March 2023

ObjectivesOur objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics.BackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear.MethodsAutopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue.ResultsWe observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels.ConclusionOur results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis, and endothelial activation as key drivers of cardiovascular events during COVID-19.
Neural network-derived perfusion maps: A model-free approach to computed tomography perfusion in patients with acute ischemic stroke
Authors: Gava Umberto A. , D’Agata Federico , Tartaglione Enzo , Renzulli Riccardo , Grangetto Marco , Bertolino Francesca , Santonocito Ambra , Bennink Edwin , Vaudano Giacomo , Boghi Andrea , Bergui Mauro 
Published: March 2023

ObjectiveIn this study, we investigate whether a Convolutional Neural Network (CNN) can generate informative parametric maps from the pre-processed CT perfusion data in patients with acute ischemic stroke in a clinical setting.MethodsThe CNN training was performed on a subset of 100 pre-processed perfusion CT dataset, while 15 samples were kept for testing. All the data used for the training/testing of the network and for generating ground truth (GT) maps, using a state-of-the-art deconvolution algorithm, were previously pre-processed using a pipeline for motion correction and filtering. Threefold cross validation had been used to estimate the performance of the model on unseen data, reporting Mean Squared Error (MSE). Maps accuracy had been checked through manual segmentation of infarct core and total hypo-perfused regions on both CNN-derived and GT maps. Concordance among segmented lesions was assessed using the Dice Similarity Coefficient (DSC). Correlation and agreement among different perfusion analysis methods were evaluated using mean absolute volume differences, Pearson correlation coefficients, Bland-Altman analysis, and coefficient of repeatability across lesion volumes.ResultsThe MSE was very low for two out of three maps, and low in the remaining map, showing good generalizability. Mean Dice scores from two different raters and the GT maps ranged from 0.80 to 0.87. Inter-rater concordance was high, and a strong correlation was found between lesion volumes of CNN maps and GT maps (0.99, 0.98, respectively).ConclusionThe agreement between our CNN-based perfusion maps and the state-of-the-art deconvolution-algorithm perfusion analysis maps, highlights the potential of machine learning methods applied to perfusion analysis. CNN approaches can reduce the volume of data required by deconvolution algorithms to estimate the ischemic core, and thus might allow the development of novel perfusion protocols with lower radiation dose deployed to the patient.
Therapeutic effects of CD133 + Exosomes on liver function after stroke in type 2 diabetic mice
Authors: Venkat Poornima , Gao Huanjia , Findeis Elizabeth L. , Chen Zhili , Zacharek Alex , Landschoot-Ward Julie , Powell Brianna , Lu Mei , Liu Zhongwu , Zhang Zhenggang , Chopp Michael 
Published: March 2023

Background and purposeNon-alcoholic fatty liver disease (NAFLD) is known to adversely affect stroke recovery. However, few studies investigate how stroke elicits liver dysfunction, particularly, how stroke in type 2 diabetes mellitus (T2DM) exacerbates progression of NAFLD. In this study, we test whether exosomes harvested from human umbilical cord blood (HUCBC) derived CD133 + cells (CD133 + Exo) improves neuro-cognitive outcome as well as reduces liver dysfunction in T2DM female mice.MethodsFemale, adult non-DM and T2DM mice subjected to stroke presence or absence were considered. T2DM-stroke mice were randomly assigned to receive PBS or Exosome treatment group. CD133 + Exo (20 μg/200 μl PBS, i.v.) was administered once at 3 days after stroke. Evaluation of neurological (mNSS, adhesive removal test) and cognitive function [novel object recognition (NOR) test, odor test] was performed. Mice were sacrificed at 28 days after stroke and brain, liver, and serum were harvested.ResultsStroke induces severe and significant short-term and long-term neurological and cognitive deficits which were worse in T2DM mice compared to non-DM mice. CD133 + Exo treatment of T2DM-stroke mice significantly improved neurological function and cognitive outcome indicated by improved discrimination index in the NOR and odor tests compared to control T2DM-stroke mice. CD133 + Exo treatment of T2DM stroke significantly increased vascular and white matter/axon remodeling in the ischemic brain compared to T2DM-stroke mice. However, there were no differences in the lesion volume between non-DM stroke, T2DM-stroke and CD133 + Exo treated T2DM-stroke mice. In T2DM mice, stroke induced earlier and higher TLR4, NLRP3, and cytokine expression (SAA, IL1β, IL6, TNFα) in the liver compared to heart and kidney, as measured by Western blot. T2DM-stroke mice exhibited worse NAFLD progression with increased liver steatosis, hepatocellular ballooning, fibrosis, serum ALT activity, and higher NAFLD Activity Score compared to T2DM mice and non-DM-stroke mice, while CD133 + Exo treatment significantly attenuated the progression of NAFLD in T2DM stroke mice.ConclusionTreatment of female T2DM-stroke mice with CD133 + Exo significantly reduces the progression of NAFLD/NASH and improves neurological and cognitive function compared to control T2DM-stroke mice.
Mentha rotundifolia (L.) Huds. aqueous extract attenuates H2O2 induced oxidative stress and neurotoxicity
Authors: Boualam Khadija , Bouhaddou Nezha , Sobeh Mansour , Tabyaoui Mohamed , Taghzouti Khalid 
Published: March 2023

IntroductionOxidative stress plays a causal role in neurodegenerative diseases. The aim of this study is to evaluate the antioxidant and neuroprotective effects ofMentha rotundifolia(L.) Huds (M. rotundifolia), a widely used Moroccan plant in traditional medicine.MethodsThe chemical composition ofM. rotundifoliaaqueous extract was analyzed by liquid chromatography coupled to mass spectrometry (LC-MS). 2,2-diphenyl 1-picrylhydrazyl (DPPH) and 2,2′-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) assays were used to assess itsin vitroantioxidant activity. H2O2was utilized to induce oxidative stress and neurotoxicityin vivo. Behavioral changes were evaluated using Open Field, Y-maze and Rotarod tests. Hyperalgesia was assessed using the tail immersion test.Results and discussionThe LC-MS/MS analysis revealed high content of kaempferol glucuronide (85%) at the extract. IC50values of the DPPH and ABTS were 26.47 and 41.21 μg/mL, respectively. Pre-treatments withM. rotundifoliaextract attenuated the behavioral changes induced by H2O2. In addition, the latency of tail withdrawal increased significantly in the treated groups suggesting central analgesic effect ofM. rotundifoliaextract. Moreover, the extract attenuated the deleterious effects of H2O2and improved all liver biomarkers. The obtained results suggested thatM. rotundifoliahad remarkable antioxidant and neuroprotective effects and may prevent oxidative stress related disorders.
Electroacupuncture and manual acupuncture at LR3 and ST36 have attenuating effects on hypertension and subsequent cognitive dysfunction in spontaneously hypertensive rats: A preliminary resting-state functional magnetic resonance imaging study
Authors: Liu Ji-peng , Li Yin-yin , Yang Ke-zhen , Shi Shu-feng , Gong Yu , Tao Zhuang , Tong Yi , Sun Jiao , Yue Bing-nan , Li Xiao-lu , Gao Xin-yu , Liu Qing-guo , Xu Meng 
Published: March 2023

IntroductionChronic hypertension may have a contributory role toward cognitive impairment. Acupuncture exerts protective effects on cognitive functions while controlling the blood pressure. However, the neural mechanism underlying the dual attenuating effect of acupuncture remains unclear. In this study, we investigated the effects of electroacupuncture (EA) and manual acupuncture (MA) on the functional activity of the brain regions of spontaneously hypertensive rats (SHRs) by through resting-state functional magnetic resonance imaging (rs-fMRI). We also evaluated the differences in these functional activities between the EA and MA groups.MethodsWe randomly assigned 30 SHRs into the EA, MA, and model (SHR) groups. Wistar Kyoto rats (n = 10) were used as normal control (WKY). The interventions were administered once every alternate day for 12 weeks. The systolic blood pressure of all rats was recorded every 2 weeks until the end of the intervention. After the intervention, rs-fMRI scanning was performed to access the whole brain data of rats randomly selected from each group evenly. The amplitude of low frequency fluctuation (ALFF) analysis, regional homogeneity (ReHo) analysis, and functional connectivity (FC) analysis were also conducted. The Morris water maze (MWM) test was conducted to evaluate the learning and memory of the rats. Hematoxylin-eosin staining and Nissl staining were performed to observe histopathological changes in the key brain regions.ResultsWe demonstrated that, when compared with the SHR group, the EA and MA groups had significantly lower blood pressure and better performance for behavioral test indices, and that the effect of EA was better than that of MA. ALFF and ReHo analyses revealed enhancement of the neuronal activity of some functionally impaired brain areas in the EA and MA groups. The main callback brain regions included the hypothalamus, entorhinal cortex, brain stem, prelimbic cortex, cingulate cortex, corpus callosum, and cerebellum. The FC analysis demonstrated that EA and MA enhanced the functional connectivity between the seeds and brain regions such as the brain stem, entorhinal cortex, hippocampus, prelimbic cortex, and cerebellum. The pathological test of the entorhinal cortex also verified the protective effect of acupuncture on the neuronal functional activity.DiscussionOur findings suggested that EA and MA exhibited attenuating effects on hypertension and cognitive dysfunction by enhancing the functional activities in the corresponding brain regions. Moreover, EA activated more callback brain regions and functional connectivity than MA, which may explain why the effect of EA was better than that of MA.
Early development of infant gut microbiota in relation to breastfeeding and human milk oligosaccharides
Authors: Chichlowski Maciej , van Diepen Janna A. , Prodan Andrei , Olga Laurentya , Ong Ken K. , Kortman Guus A. M. , Dunger David B. , Gross Gabriele 
Published: March 2023

BackgroundInfant gut microbiota composition is influenced by various factors early in life. Here, we investigate associations between infant gut microbiome development, infant age, breastfeeding duration, and human milk oligosaccharides (HMO) composition in breastmilk.MethodsA total of 94 mother-infant pairs were recruited as part of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) (Cambridge, UK). Infant stool samples (n= 337) were collected at 2 week, 6 week, 3 month, and 6 month of age. The 16S rRNA V3-V4 rRNA region was sequenced using MiSeq Illumina to determine microbiota composition and diversity. Mother’s hindmilk samples were collected at birth, 2 week, 6 week, 3 month, and 6 month postpartum. Concentrations of five neutral [2′FL, 3′FL, lacto-N-fucopentaose 1 (LNFP1), LNnT, LNT] and two acidic (3′SL, and 6′SL) HMOs were measured in all milk samples using High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD). We explored the associations between infant gut microbiome parameters and age, duration of exclusive breastfeeding (EBF), and levels of individual HMOs.ResultsBifidobacteriumwas the most abundant genus in infant stool at all-time points, irrespective of breastfeeding duration, with an overall mean relative abundance of 70%. The relative abundance ofB. bifidumin stool from infants who were breastfed for longer than 6 months was significantly higher compared to the infant breastfed up to 3 months (p= 0.0285). Alpha-diversity (both Shannon and ASV-level Richness) of infant gut microbiota showed a biphasic change with infant age, decreasing from 2 weeks until 3 months and then increasing until 6 months of age.Bifidobacteriumrelative abundance was associated with higher concentrations of 2′FL and LNFP1 in breastmilk across all time-points (p= 0.049 and 0.017, respectively), with trends toward a higher abundance ofB. longumspecies. No significant association withBifidobacteriumwas found for breastmilk LNnT, 3′SL, and 6′SL levels.ConclusionOur study is in line with previous data demonstrating that EBF duration in the first months of life impacts infant gut microbiota composition. The observed links between specific HMOs in breastmilk and bacteria in infant stool provide evidence of how mother’s milk affects infant microbiome development.
Documentation of the evidence-diagnosis link predicts nutrition diagnosis resolution in the Academy of Nutrition and Dietetics' diabetes mellitus registry study: A secondary analysis of Nutrition Care Process outcomes
Authors: Colin Casey , Arikawa Andrea , Lewis Sherri , Cooper Melissa , Lamers-Johnson Erin , Wright Lauri , Papoutsakis Constantina 
Published: March 2023

ObjectivesTo describe nutrition care documentation patterns and investigate predictors of nutrition diagnosis resolution.MethodsThis is a secondary data analysis of a 2-year pragmatic, quasi-experimental study conducted in outpatient clinics where nutrition care was provided to adults with diabetes Type 1 or 2 from May 2017 to June 2019 (n = 564 patients). The main outcome measures were frequency of standardized Nutrition Care Process (NCP) terms, NCP links, nutrition diagnosis resolution and predictors of nutrition diagnosis resolution. Predictors of diagnosis resolution were identified using a multivariable logistic regression model.ResultsThe most prevalent resolved diagnoses were excessive carbohydrate intake (32%), undesirable food choices (21%) and excessive energy intake (13%). The top etiology was food and nutrition related knowledge deficit (57%) and interventions were drawn mainly from the Nutrition Education domain (64%). One hundred forty-six patient cases (26%) had at least one follow-up visit and 26% of those with a follow-up (n = 38) had a resolved diagnosis. The presence of the evidence-diagnosis NCP link in documentation predicted diagnosis resolution (OR = 2.80, 95% CI 1.30–6.02; p = 0.008).ConclusionMost diagnoses were caused by patients' lack of knowledge and respective interventions focused on nutrition education. Odds of diagnosis resolution improved when the signs and symptoms of the diagnosis were documented during assessment (evidence-diagnosis NCP link). Training dietitians on NCP links may be important to resolve nutrition diagnoses. Presented findings are hypothesis generating.