bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crosstalk Between the Gut and Brain: Importance of the Fecal Microbiota in Patient With Brain Tumors
Authors: Li Yuping , Jiang Haixiao , Wang Xiaolin , Liu Xiaoguang , Huang Yujia , Wang Zhiyao , Ma Qiang , Dong Lun , Qi Yajie , Zhang Hengzhu , Lu Guangyu 
Published: June 2022

BackgroundVariations in the gut microbiota may affect the metabolism, inflammation and immune response of the host. Microbiota dysbiosis has been extensively investigated in neurological disorders and diseases of the central nervous system (CNS). However, the alterations of the gut microbiota in patients suffering from brain tumors and the associations of the gut microbiota with these diseases remain unknown. Herein, we investigate the alterations of the gut microbiota community in patients with brain tumors and the associations between the two and further explore microbial markers used for the diagnosis of brain tumors.MethodsIn our study, we recruited 158 participants, consisting of 101 brain tumor patients (65 benign and 36 malignant cases) and 57 age- and sex-matched healthy controls (HCs). We characterized the gut microbial community by using 16S rRNA gene amplicon sequencing and investigated its correlations with clinical features.ResultsThe results showed remarkably less microbial ecosystem richness and evenness in patients with brain tumors than in HCs. The gut microbiota community structure underwent profound changes in the brain tumor group, including an increase in the abundances of pathogenic bacteria, such as Fusobacteriota and Proteobacteria and a reduction in the abundances of probiotic bacteria, such as Bifidobacterium or Lachnospira. Moreover, our study indicated more significant correlations and clustering of pathogens in the malignant brain tumor group. Furthermore, a biomarker panel was used to discriminate the brain tumor patients from the healthy controls (AUC: 0.77). Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation revealed an accumulation of harmful metabolites and disorders of the basic physiological pathways in the brain tumor group.ConclusionsOur study revealed that brain tumor patients may possess divergent host-microbe interactions from those of healthy controls, especially in malignant brain tumor patients. In addition, the intestinal flora may be involved in immune responses and metabolism in the microenvironment of brain tumors. All evidence, including the biomarker panel, suggests that the intestinal flora may be a useful diagnostic and predictive tool and an important preventive target for brain tumors.
Short- and Long-Term Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Left Ventricular Remodeling in Patients Early After ST-Segment Elevation Myocardial Infarction—The HIIT-EARLY Randomized Controlled Trial
Authors: Eser Prisca , Trachsel Lukas D. , Marcin Thimo , Herzig David , Freiburghaus Irina , De Marchi Stefano , Zimmermann Andreas J. , Schmid Jean-Paul , Wilhelm Matthias 
Published: June 2022

AimDue to insufficient evidence on the safety and effectiveness of high-intensity interval training (HIIT) in patients early after ST-segment elevation myocardial infarction (STEMI), we aimed to compare short- and long-term effects of randomized HIIT or moderate-intensity continuous training (MICT) on markers of left ventricular (LV) remodeling in STEMI patients receiving optimal guideline-directed medical therapy (GDMT).Materials and MethodsPatients after STEMI (&lt;4 weeks) enrolled in a 12-week cardiac rehabilitation (CR) program were recruited for this randomized controlled trial (NCT02627586). During a 3-week run-in period with three weekly MICT sessions, GDMT was up-titrated. Then, the patients were randomized to HIIT or isocaloric MICT for 9 weeks. Echocardiography and cardiopulmonary exercise tests were performed after run-in (3 weeks), end of CR (12 weeks), and at 1-year follow-up. The primary outcome was LV end-diastolic volume index (LVEDVi) at the end of CR. Secondary outcomes were LV global longitudinal strain (GLS) and cardiopulmonary fitness.ResultsSeventy-three male patients were included, with the time between STEMI and start of CR and randomization being 12.5 ± 6.3 and 45.8 ± 10.8 days, respectively. Mixed models revealed no significant group × time interaction for LVEDVi at the end of CR (p = 0.557). However, there was a significantly smaller improvement in GLS at 1-year follow-up in the HIIT compared to the MICT group (p = 0.031 for group × time interaction). Cardiorespiratory fitness improved significantly from a median value of 26.5 (1st quartile 24.4; 3rd quartile 1.1) ml/kg/min at randomization in the HIIT and 27.7 (23.9; 31.6) ml/kg/min in the MICT group to 29.6 (25.3; 32.2) and 29.9 (26.1; 34.9) ml/kg/min at the end of CR and to 29.0 (26.6; 33.3) and 30.6 (26.0; 33.8) ml/kg/min at 1 year follow-up in HIIT and MICT patients, respectively, with no significant group × time interactions (p = 0.138 and 0.317).ConclusionIn optimally treated patients early after STEMI, HIIT was not different from isocaloric MICT with regard to short-term effects on LVEDVi and cardiorespiratory fitness. The worsening in GLS at 1 year in the HIIT group deserves further investigation, as early HIIT may offset the beneficial effects of GDMT on LV remodeling in the long term.
Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC–MS-Based Untargeted Metabolomics Study
Authors: Lijing Wang , Sujie Ke , Linxi Wang , Lishan Huang , Liqin Qi , Zhidong Zhan , Kejun Wu , Mengjun Zhang , Xiaoying Liu , Xiaohong Liu , Libin Liu 
Published: June 2022

BackgroundRecurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia; the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies.MethodsWe screened 553 community-based T2DM patients. T2DM with RH (DH group, n=40) and T2DM without hypoglycemia (DC group, n=40) were assigned in the case-control study, matched by propensity score matching. Non-targeted, global metabolite profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry. Principal component analysis and supervised projections to latent structures-discriminant analysis were constructed to evaluate the potential biomarkers. Metabolites with a fold change of &gt;2.0 or &lt;0.5, a t-test q-value &lt;0.05, and variable importance in projection value of &gt;1 were identified as significantly differential metabolites. MetaboAnalyst was performed to analyze the related metabolic pathways.ResultsWe identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways; the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all q &lt;0.05) were significantly lower during RH. The combination of these metabolites can serve as a reliable predictor biomarker for RH (area under the curve = 0.88). Regarding lipid metabolism, triglyceride was upregulated (P=0.003) and the O-Acylcarnitine was downregulated (q &lt; 0.001). Besides, RH was accompanied by lower phenylalanine (q=0.003) and higher cortisone (q=0.005) levels.ConclusionsRH in T2DM is accompanied by caffeine, lipolysis, phenylalanine, and cortisone metabolism abnormalities. Caffeine might be a reliable candidate biomarker and potential prevention strategy for RH, but further validation studies are needed.Clinical Trial RegistryChi CTR 1900026361, 2019-10-3.
Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis
Authors: Jeffreys Sarah A. , Becker Therese M. , Khan Sarah , Soon Patsy , Neubauer Hans , de Souza Paul , Powter Branka 
Published: June 2022

BackgroundUp to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors). CCND1 encodes the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle. CCND1 amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of CCND1 amplification on estrogen receptor positive patients’ disease outcomes, is vital. This review aims to evaluate CCND1 amplification as a prognostic and predictive biomarker in BCa.Materials and MethodsPublications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language, in vitro and animal studies, not BCa, male BCa, premenopausal BCa, cohort size &lt;35, CCND1 amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is [CRD42020208179].ResultsCCND1 amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001). CCND1 amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically, CCND1 amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p &lt; 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.ConclusionWhile a lack of standardised approach for the detection of CCND1 amplification is to be considered as a limitation, CCND1 amplification was found to be prognostic of shorter RFS and OS in BCa. CCND1 amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of CCND1 amplification, CCND1 amplification would have potential as a predictive biomarker in breast cancer patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020208179.
Validating and Comparing C-TIRADS, K-TIRADS and ACR-TIRADS in Stratifying the Malignancy Risk of Thyroid Nodules
Authors: Chen Qingfang , Lin Mingnan , Wu Size 
Published: June 2022

The thyroid imaging reporting and data system (TIRADS) was proposed by experts for optimal ultrasound evaluation of malignancy risk of thyroid focal lesions. There are several versions of TIRADS, some of them have been validated sufficiently, and the others have not been well assessed. In this study, a recently launched Chinese version of TIRADS (C-TIRADS) for malignancy risk stratification of thyroid nodules was validated, and the performance was compared to that of the Korean TIRADS (K-TIRADS) and American College of Radiology(ACR) TIRADS (ACR-TIRADS). Archives of 2177 patients who had undergone thyroid ultrasound examination, coarse needle tissue biopsy and/or surgery were reviewed, and 1978 patients with 1982 thyroid nodules were assessed according to the three TIRADSs. The histopathology was taken as the golden standard. The results showed the 1982 thyroid nodules were consisted of 1306 benign nodules and 676 malignant nodules. The malignancy risk accounted for 1.09%, 2.14%, 10.34%, 49.28%, 88.19% and 85.29% of the total nodules that were categorised as C-TIRADS 2, 3, 4A, 4B, 4C and 5, respectively; 0.00%, 1.64%, 2.87%,18.71% and 82.22% of the total nodules that were categorised as ACR-TIRADS 1, 2, 3, 4 and 5, respectively; 0.85%, 3.27%, 24.27% and 80.96% of the total nodules that were categorised as K-TIRADS 2, 3, 4 and 5, respectively. The correlation between the category of TIRADS and percentile of malignancy was 0.94 in the C-TIRADS, 1.00 in the ACR-TIRADS, and 1.00 in the K-TIRADS, respectively. The highest values of accuracy(AUC) of ROC curves of C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 were taken as the cut-off values for risk stratification, respectively. The sensitivity, specificity, positive and negative predictive values and AUC by C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 for malignancy risk stratification of thyroid nodules were 90.83%, 84.23%, 74.88% and 94.66% and 0.88, respectively; 83.58%, 89.82%, 80.95%, 91.36% and 0.87, respectively; and 85.50%, 90.35%, 82.10%, 92.33% and 0.88, respectively (P&gt;0.05 for all). We concluded that the C-TIRADS has excellent performance in the malignancy risk stratification of thyroid nodules by the optimized cut-off value, which is comparable to that in K-TIRADS and ACR-TIRADS.
Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells
Authors: La Manna Marco Pio , Shekarkar Azgomi Mojtaba , Tamburini Bartolo , Badami Giusto Davide , Mohammadnezhad Leila , Dieli Francesco , Caccamo Nadia 
Published: June 2022

The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases.Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as “memory”.T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8+TRMand TSCMcells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases.
Dabigatran and Wet AMD, Results From Retinal Pigment Epithelial Cell Monolayers, the Mouse Model of Choroidal Neovascularization, and Patients From the Medicare Data Base
Authors: Akter Tanjina , Annamalai Balasubramaniam , Obert Elisabeth , Simpson Kit N. , Rohrer Bärbel 
Published: June 2022

BackgroundAge-related macular degeneration (AMD), the leading cause of irreversible blindness in elderly Caucasian populations, includes destruction of the blood-retina barrier (BRB) generated by the retinal pigment epithelium-Bruch’s membrane complex (RPE/BrM), and complement activation. Thrombin is likely to get access to those structures upon BRB integrity loss. Here we investigate the potential role of thrombin in AMD by analyzing effects of the thrombin inhibitor dabigatran.Material and MethodsMarketScan data for patients aged ≥65 years on Medicare was used to identify association between AMD and dabigatran use. ARPE-19 cells grown as mature monolayers were analyzed for thrombin effects on barrier function (transepithelial resistance; TER) and downstream signaling (complement activation, expression of connective tissue growth factor (CTGF), and secretion of vascular endothelial growth factor (VEGF)). Laser-induced choroidal neovascularization (CNV) in mouse is used to test the identified downstream signaling.ResultsRisk of new wet AMD diagnosis was reduced in dabigatran users. In RPE monolayers, thrombin reduced TER, generated unique complement C3 and C5 cleavage products, led to C3d/MAC deposition on cell surfaces, and increased CTGF expression via PAR1-receptor activation and VEGF secretion. CNV lesion repair was accelerated by dabigatran, and molecular readouts suggest that downstream effects of thrombin include CTGF and VEGF, but not the complement system.ConclusionsThis study provides evidence of association between dabigatran use and reduced exudative AMD diagnosis. Based on the cell- and animal-based studies, we suggest that thrombin modulates wound healing and CTGF and VEGF expression, making dabigatran a potential novel treatment option in AMD.
Derivation and Validation of a New Disease Activity Assessment Tool With Higher Accuracy for Takayasu Arteritis
Authors: Kwon Oh Chan , Park Min-Chan 
Published: June 2022

ObjectiveTo develop a new disease activity assessment tool with high accuracy for Takayasu arteritis.MethodsIndividual items from National Institute of Health (NIH) criteria and the Indian Takayasu Clinical Activity Score (ITAS2010) were tested as candidate variables to develop a new disease activity assessment tool in a derivation cohort (N = 100). Physician global assessment on disease activity was used as the gold standard. Multivariable logistic regression models were constructed and the model with the highest accuracy was identified. A formula assessing disease activity was generated using simplified β coefficients (rounded to decimal place). Diagnostic performance was evaluated through estimating the area under the curve (AUC). The new assessment tool was subsequently validated in a validation cohort (N = 46).ResultsThe multivariable model yielding the highest accuracy consisted of a high erythrocyte sedimentation rate (ESR), NIH criteria 1 and 4, and carotidynia. Using simplified β coefficients, the following disease activity assessment tool was developed: high ESR (3 points), NIH criterion 1 (2 points), NIH criterion 4 (4 points), and carotidynia (3 points) (total score ≥5, active; total score &lt;5, inactive). The new disease activity assessment tool had a higher AUC (89.37) for discriminating active and inactive diseases than NIH criteria (AUC 77.96), ITAS2010 (AUC 66.12), ITAS-ESR (AUC 75.58), and ITAS-C-reactive protein (AUC 71.34). The AUC (85.23) of the new assessment tool was similar in the validation cohort.ConclusionA new disease activity assessment tool that consists of high ESR, NIH criteria 1 and 4, and carotidynia had higher accuracy in discriminating active and inactive disease than currently used clinical assessment tools.
Metagenomic Next-Generation Sequencing Is Highly Efficient in Diagnosing Pneumocystis Jirovecii Pneumonia in the Immunocompromised Patients
Authors: Wang Dongsheng , Fang Shihua , Hu Xiaowen , Xu Qixia , Chu Xinmin , Mei Xiaodong , Xie Wang 
Published: June 2022

PurposesTo explore the value of metagenomic next-generation sequencing (mNGS) in diagnosing pneumocystis jiroveciipneumonia (PJP) in the immunocompromised patients.MethodsData of 122 patients with PJP in an immunosuppressed state and 67 non-PJP patients were collected. The diagnostic efficacy of mNGS was compared with the conventional methods, including Gomori methenamine silver (GMS) staining and serum (1,3)-β-D-glucan (BDG). Changes of anti-microbial therapy for patients with PJP based on mNGS results were also reviewed.ResultsThe diagnostic sensitivity of mNGS to PJP was higher than that of GMS and BDG (100% vs. 15 and 74.5%, p &lt; 0.001). The diagnostic specificity (91.%) was lower than that of GMS (100%), and similar with BDG (89.6%). In addition to P. jirovecii, mNGS revealed co-pathogens like human β-herpesvirus 5, human γ-pesvirus 4, and some other opportunistic pathogens. The reads of mNGS were remarkably higher in BALF than in blood samples. Initial antimicrobial treatment was modified in 89.3% patients based on the mNGS results, and 74 cases (60.7%) were treated with anti-P. jirovecii therapy.ConclusionmNGS is highly efficient in diagnosing PJP and good at identifying pathogens in mixed infections.
Exercise for Stroke Rehabilitation: A Bibliometric Analysis of Global Research From 2001 to 2021
Authors: Dong Yulin , Weng Linman , Hu Yinhu , Mao Yuxing , Zhang Yajuan , Lu Zefeng , Shi Tingting , Du Renren , Wang Wu , Wang Jinyan , Wang Xueqiang 
Published: June 2022

ObjectiveTo make a bibliometric analysis of global trends in research into exercise interventions for stroke between 2001 and 2021.MethodThis study did the systematic literature from 2001 to 2021 in Web of Science Core Collection. CiteSpace software was used to analyze the relationship of publications with countries, journals, authors, references, and keywords.ResultsA total of 3,484 publications were obtained in the bibliometric analysis. The number of publications increased gradually over the period. The United States have the most number of publications. The journal stroke had the most citations per paper (106.95) and the highest impact factor (IF 2020, 7.194). The most high frequency keywords are “stroke,” “rehabilitation,” and “recovery,” the top of burst key words are “health,” “speed,” and “aerobic exercise”.ConclusionThese findings provide the trends of exercise for stroke s and provided the potential research frontiers in the past 20 years. It will be a useful basis for further research into focus issues, cooperators, development trends.
The Seasonal Fluctuation of Fatigue in Multiple Sclerosis
Authors: Grothe Matthias , Gross Stefan , Süße Marie , Strauss Sebastian , Penner Iris Katharina 
Published: June 2022

BackgroundFatigue is a common symptom in patients with multiple sclerosis. Several studies suggest that outdoor temperature can impact fatigue severity, but a systematic study of seasonal variations is lacking.MethodsFatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC) in a temperate climatic zone with an average outdoor temperature of 8.8°C. This study included 258 patients with multiple sclerosis from 572 visits temporally distributed over the year. The data were adjusted for age, sex, cognition, depression, disease severity, and follow-up time. Linear regression models were performed to determine whether the temporal course of fatigue was time-independent, linearly time dependent, or non-linearly time dependent.ResultsFatigue was lowest during January (mean FSMC: 49.84) and highest during August (mean FSMC: 53.88). The regression analysis showed the best fit with a model that included months + months2, which was a non-linear time dependency. Mean FSMC per month correlated significantly with the average monthly temperature (ρ = 0.972; p &lt; 0.001).ConclusionIn multiple sclerosis, fatigue showed a natural temporal fluctuation. Fatigue was higher during summer compared to winter, with a significant relationship of fatigue with outdoor temperature. This finding should be carefully taken into account when clinically monitoring patients over time to not interpret higher or lower scores independent of seasonal aspects.