bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency
Authors: Jiang Lingling , Fei Haiyi , Tong Jinfei , Zhou Jiena , Zhu Jiajuan , Jin Xiaoying , Shi Zhan , Zhou Yan , Ma Xudong , Yu Hailan , Yang Jianhua , Zhang Songying 
Published: December 2021

ObjectiveWe explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.MethodsFecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman’s rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.ResultsThe abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.ConclusionsThe interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.
Genetic Drift Versus Climate Region Spreading Dynamics of COVID-19
Authors: Di Pietro R. , Basile M. , Antolini L. , Alberti S. 
Published: December 2021

Background: The current propagation models of COVID-19 are poorly consistent with existing epidemiological data and with evidence that the SARS-CoV-2 genome is mutating, for potential aggressive evolution of the disease.Objectives: We looked for fundamental variables that were missing from current analyses. Among them were regional climate heterogeneity, viral evolution processes versus founder effects, and large-scale virus containment measures.Methods: We challenged regional versus genetic evolution models of COVID-19 at a whole-population level, over 168,089 laboratory-confirmed SARS-CoV-2 infection cases in Italy, Spain, and Scandinavia at early time-points of the pandemic. Diffusion data in Germany, France, and the United Kingdom provided a validation dataset of 210,239 additional cases.Results: Mean doubling time of COVID-19 cases was 6.63 days in Northern versus 5.38 days in Southern Italy. Spain extended this trend of faster diffusion in Southern Europe, with a doubling time of 4.2 days. Slower doubling times were observed in Sweden (9.4 days), Finland (10.8 days), and Norway (12.95 days). COVID-19 doubling time in Germany (7.0 days), France (7.5 days), and the United Kingdom (7.2 days) supported the North/South gradient model. Clusters of SARS-CoV-2 mutations upon sequential diffusion were not found to clearly correlate with regional distribution dynamics.Conclusion: Acquisition of mutations upon SARS-CoV-2 spreading failed to explain regional diffusion heterogeneity at early pandemic times. Our findings indicate that COVID-19 transmission rates are rather associated with a sharp North/South climate gradient, with faster spreading in Southern regions. Thus, warmer climate conditions may not limit SARS-CoV-2 infectivity. Very cold regions may be better spared by recurrent courses of SARS-CoV-2 infection.
The Role of EUPATI CH in Promoting Patient Involvement in Clinical Research: A Multi-Stakeholder Research Project
Authors: Sessa Cristiana , Schmid Caecilia , Tolotti Angela , Magnin Annette , Haerry David , Bonetti Loris , Klingmann Ingrid 
Published: December 2021

Background: The European Patients' Academy on Therapeutic Innovation Switzerland (EUPATI CH) was established as an association in 2016 with the mission to improve patient empowerment in Switzerland, raise public awareness of EUPATI's education material, and foster multi-stakeholder partnerships in order to promote public involvement in all aspects of medicines research and development (R&amp;D). In order to achieve its goal of improving patient involvement (PI) in all processes of medicines R&amp;D in Switzerland and to obtain guidance and recommendations for future activities, EUPATI CH initiated a multi-stakeholder survey on PI experiences, hurdles, and best practices. The survey enabled EUPATI CH to obtain and analyze the views of various stakeholders and shape its workplan.Methods: Data collection occurred between January and July 2019 using a survey and semi-structured interviews with individual stakeholders from different groups. The online survey responses were analyzed using quantitative methods and the interviews were analyzed using qualitative methods.Results: The online survey was completed by 55 respondents (10%), and the semi-structured interviews were conducted with 14 stakeholders. Respondents to the online survey were patient representatives (45%), researchers from academia (25%), individuals from the pharmaceutical industry (9%), healthcare professionals (23%), and representatives from government agencies (6%). Some respondents were also members of EUPATI CH. Thirty-eight percent of respondents consider PI in Switzerland to be limited or absent. They identified the main barriers to PI as, first and foremost, a lack of funds and human resources (65%), followed by a lack of information and a lack of education on how to become a patient advocate (21%), a lack of collaboration with other stakeholders (16%), and a lack of adequate resources. Respondents' expectations of EUPATI CH's role in supporting PI were to provide education for active PI and improve networking and collaboration among stakeholders.Conclusions: EUPATI CH's multi-stakeholder research identified some of the difficulties in promoting PI in medicines R&amp;D in Switzerland, in particular the complex collaboration among stakeholders and a lack of funds, human resources, and knowledge. To respond to these difficulties, EUPATI CH has begun preparing a basic training course for patients that is adapted to Switzerland.
Zoledronic Acid for Periprosthetic Bone Mineral Density Changes in Patients With Osteoporosis After Hip Arthroplasty—An Updated Meta-Analysis of Six Randomized Controlled Trials
Authors: Liu Yuan , Xu Jia-Wen , Li Ming-Yang , Wu Li-Min , Zeng Yi , Shen Bin 
Published: December 2021

Introduction:Periprosthetic bone mineral density (BMD) loss following total hip arthroplasty (THA) may threaten the survival of the implant, especially in patients with osteoporosis. Zoledronic acid (ZA) is the representative of the third generation of bisphosphonates, which were effective in reducing bone loss in conditions associated with accelerated bone turnover. The aim of this study was to evaluate the efficacy and safety of ZA in patients with osteoporosis after THA.Methods:Randomized controlled trials (RCTs) associated with ZA and THA were searched from the MEDLINE, PubMed, EMBASE, Wanfang database, and the Web of Science (August 2021). Other methods, such as hand search and email request were also tried. The methodological quality was assessed by the Risk of Bias (RoB) 2.0. Relevant data were abstracted from the included RCTs and authors were contacted when necessary.Results:In this study, six RCTs involving a total of 307 patients were finally included and analyzed. The pooled data demonstrated that significantly less periprosthetic BMD loss in Gruen zone seven had occurred in the ZA-treated patients than in the control patients at 3 months (mean difference [MD] = 4.03%; 95%CI: 0.29–7.76%;P= 0.03), 6 months (MD = 7.04%; 95%CI: 2.12–11.96%;P= 0.005), and 12 months (MD = 7.12%; 95%CI: 0.33–13.92%;P= 0.04). The Harris Hip Score (HHS) was also significantly increased in ZA group at 6 and 12 months after operation (P= 0.03 andP= 0.02, respectively). Influenza-like symptom was found related to the usage of ZA [relative risk (RR) = 7.03,P&lt; 0.0001].Conclusion:A meta-analysis of six RCTs suggested that ZA was beneficial in maintaining the periprosthetic BMD in patients with osteoporosis at 6 and 12 months after THA. In addition, the HHS was significantly improved in patients treated with ZA. However, the short length of follow-up of the available studies resulted in the lack of analyses regarding the survival of implants including the rate of aseptic loosing, periprosthetic fracture, and revision. It still needs to be determined in research with longer follow-up period.Clinical Trial Registration:Researchregistry.com, identifier: reviewregistry1087.
Involvement of Small Colony Variant-Related Heme Biosynthesis Genes in Staphylococcus aureus Persister Formation in vitro
Authors: Wang Xuyang , Li Weizheng , Wang Wenjie , Wang Shiyong , Xu Tao , Chen Jiazhen , Zhang Wenhong 
Published: December 2021

Background: Persisters are important reasons for persistent infections, and they can lead to antibiotic treatment failure in patients and consequently chronic infection. Staphylococcus aureus small colony variants (SCVs) have been shown to be related to persistent infection. Mutations in the genes of the heme biosynthesis pathway lead to the formation of SCVs. However, the relationship between heme production genes and persister has not been tested.Methods:HemA and hemB were knocked out by allelic replacement from S. aureus strain USA500 separately, and then, the heme deficiency was complemented by overexpression of related genes and the addition of hemin. The stress-related persister assay was conducted. RNA-sequencing was performed to find genes and pathways involved in heme-related persister formation, and relative genes and operons were further knocked out and overexpressed to confirm their role in each process.Results: We found that heme biosynthesis deficiency can lead to decreased persister. After complementing the corresponding genes or hemin, the persister levels could be restored. RNA-seq on knockout strains showed that various metabolic pathways were influenced, such as energy metabolism, amino acid metabolism, carbohydrate metabolism, and membrane transport. Overexpression of epiF and operon asp23 could restore USA500∆hemA persister formation under acid stress. Knocking out operon arc in USA500∆hemA could further reduce USA500∆hemA persister formation under acid and oxidative stress.Conclusion: Heme synthesis has a role in S. aureus persister formation.
The Role of the Diaphragm in Postural Stability and Visceral Function in Parkinson’s Disease
Authors: Yu Xin , Jiang Hong-ying , Zhang Chen-xi , Jin Zhao-hui , Gao Lei , Wang Rui-dan , Fang Jin-ping , Su Yuan , Xi Jia-ning , Fang Bo-yan 
Published: December 2021

Background: In normal subjects, the diaphragm plays a key functional role in postural stability, articulation, respiration, defecation, and urination.Objectives: The aim of this study was to investigate the role of the diaphragm in postural stability and visceral function in patients with Parkinson’s disease (PD) and to compare the diaphragm function by gender, Hoehn and Yahr (H&amp;Y) staging, and motor subtypes.Methods: In total, 79 patients were enrolled in this cross-sectional study. The severity of the disease was assessed by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale III and by H&amp;Y staging. Postural stability was quantitatively recorded, and respiratory function was evaluated by spirometry. Several scales were used to evaluate visceral function in patients with PD. In addition, diaphragm ultrasound was used to measure the excursion, contraction velocity, and thickness of the diaphragm during quiet breathing, deep breathing, and the sniff test. Significant features were selected by the least absolute shrinkage and selection operator (LASSO) regression and fitted in the multivariate linear regression and Pearson’s correlation analysis.Results: Diaphragm thickness and excursion during quiet breathing were significantly different between men and women and between H&amp;Y stage 1–2 and stage 2.5–3, whereas the diaphragm function was not influenced by motor subtypes. It was shown that the diaphragmatic function was significantly correlated with postural stability, voice function, respiratory function, constipation, and urological function to varying degrees in patients with PD.Conclusion: The diaphragmatic function is associated with dysfunction in PD although it remains unclear as to whether the observed changes in the diaphragm are primary or secondary.
China Registry Study on Cognitive Impairment in the Elderly: Protocol of a Prospective Cohort Study
Authors: Zhu Yingying , Pan Dong , He Lei , Rong Xiaoming , Li Honghong , Li Yi , Pi Yaxuan , Xu Yongteng , Tang Yamei 
Published: December 2021

Introduction: To develop appropriate strategies for early diagnosis and intervention of cognitive impairment, the identification of minimally invasive and cost-effective biomarkers for the early diagnosis of cognitive impairment is crucial and desirable. Therefore, the CHina registry study on cOgnitive imPairment in the Elderly (HOPE) study is designed to investigate the natural course of cognitive decline and explore the clinical, imaging, and biochemical markers for the detection and diagnosis of cognitive impairment on its earliest stage.Methods: Approximately 5,000 Chinese elderly aged more than 50 years were recruited from Sun Yat-sen Memorial Hospital, Sun Yat-sen University in Guangzhou, China by the year 2024. All subjects were invited to complete the clinical assessment, neuropsychological assessment, the biological samples collection (blood and cerebrospinal fluid (CSF)], magnetic resonance imaging (MRI) examination, and optional amyloid and tau PET. The follow-up survey was conducted every 1 year to repeat these assessments for 20 years. To better clarify the relationship between potential risk factors and endpoint events [changes in cognitive score or incidence of mild cognitive impairment (MCI) and/or dementia], appropriate statistical methods were used to analyze the data, including but not limited to, such as linear mixed-effect model, competing risk model, or the least absolute shrinkage and selection operator model.Significance: The CHina registry study on cOgnitive imPairment in the Elderly study is designed to explore the longitudinal changes in characteristics of participants with cognitive decline and to identify potential plasma and imaging biomarkers with cost-benefit and scalability advantages. The results will enable broader clinical access and efficient population screening and then improve the development of treatment and the quality of life for cognitive impairment at the early stage.Trial registration number: NCT04360200.
The Individual Ictal Fingerprint: Combining Movement Measures With Ultra Long-Term Subcutaneous EEG in People With Epilepsy
Authors: Kjaer Troels W. , Remvig Line S. , Helge Asbjoern W. , Duun-Henriksen Jonas 
Published: December 2021

Background: Epileptic seizures are caused by abnormal brain wave hypersynchronization leading to a range of signs and symptoms. Tools for detecting seizures in everyday life typically focus on cardiac rhythm, electrodermal activity, or movement (EMG, accelerometry); however, these modalities are not very effective for non-motor seizures. Ultra long-term subcutaneous EEG-devices can detect the electrographic changes that do not depend on clinical changes. Nonetheless, this also means that it is not possible to assess whether a seizure is clinical or subclinical based on an EEG signal alone. Therefore, we combine EEG and movement-related modalities in this work. We focus on whether it is possible to define an individual “multimodal ictal fingerprint” which can be exploited in different epilepsy management purposes.Methods: This study used ultra long-term data from an outpatient monitoring trial of persons with temporal lobe epilepsy obtained with a subcutaneous EEG recording system. Subcutaneous EEG, an EMG estimate and chest-mounted accelerometry were extracted from four persons showing more than 10 well-defined electrographic seizures each. Numerous features were computed from all three modalities. Based on these, the Gini impurity measure of a Random Forest classifier was used to select the most discriminative features for the ictal fingerprint. A total of 74 electrographic seizures were analyzed.Results: The optimal individual ictal fingerprints included features extracted from all three tested modalities: an acceleration component; the power of the estimated EMG activity; and the relative power in the delta (0.5–4 Hz), low theta (4–6 Hz), and high theta (6–8 Hz) bands of the subcutaneous EEG. Multimodal ictal fingerprints were established for all persons, clustering seizures within persons, while separating seizures across persons.Conclusion: The existence of multimodal ictal fingerprints illustrates the benefits of combining multiple modalities such as EEG, EMG, and accelerometry in future epilepsy management. Multimodal ictal fingerprints could be used by doctors to get a better understanding of the individual seizure semiology of people with epilepsy. Furthermore, the multimodal ictal fingerprint gives a better understanding of how seizures manifest simultaneously in different modalities. A knowledge that could be used to improve seizure acknowledgment when reviewing EEG without video.
Comprehensive Analysis of the Prognostic Values of the TRIM Family in Hepatocellular Carcinoma
Authors: Dai Weiyu , Wang Jing , Wang Zhi , Xiao Yizhi , Li Jiaying , Hong Linjie , Pei Miaomiao , Zhang Jieming , Yang Ping , Wu Xiaosheng , Tang Weimei , Jiang Xiaoling , Jiang Ping , Xiang Li , Li Aimin , Lin Jianjiao , Liu Side , Wang Jide 
Published: December 2021

BackgroundAccumulating studies have demonstrated the abnormal expressions and prognostic values of certain members of the tripartite motif (TRIM) family in diverse cancers. However, comprehensive prognostic values of the TRIM family in hepatocellular carcinoma (HCC) are yet to be clearly defined.MethodsThe prognostic values of the TRIM family were evaluated by survival analysis and univariate Cox regression analysis based on gene expression data and clinical data of HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression profiles, protein–protein interaction among the TRIM family, prediction of transcription factors (TFs) or miRNAs, genetic alterations, correlations with the hallmarks of cancer and immune infiltrates, and pathway enrichment analysis were explored by multiple public databases. Further, a TRIM family gene-based signature for predicting overall survival (OS) in HCC was built by using the least absolute shrinkage and selection operator (LASSO) regression. TCGA–Liver Hepatocellular Carcinoma (LIHC) cohort was used as the training set, and GSE76427 was used for external validation. Time-dependent receiver operating characteristic (ROC) and survival analysis were used to estimate the signature. Finally, a nomogram combining the TRIM family risk score and clinical parameters was established.ResultsHigh expressions of TRIM family members including TRIM3, TRIM5, MID1, TRIM21, TRIM27, TRIM32, TRIM44, TRIM47, and TRIM72 were significantly associated with HCC patients’ poor OS. A novel TRIM family gene-based signature (including TRIM5, MID1, TRIM21, TRIM32, TRIM44, and TRIM47) was built for OS prediction in HCC. ROC curves suggested the signature’s good performance in OS prediction. HCC patients in the high-risk group had poorer OS than the low-risk patients based on the signature. A nomogram integrating the TRIM family risk score, age, and TNM stage was established. The ROC curves suggested that the signature presented better discrimination than the similar model without the TRIM family risk score.ConclusionOur study identified the potential application values of the TRIM family for outcome prediction in HCC.
A Retrospective Analysis of the Effect of Anlotinib in Patients With Lung Cancer With or Without Previous Antiangiogenic Therapy
Authors: Suo Jiaojiao , Sun Yu , Fu Yan , Xiu Weigang , Zhang Xuanwei , Wang Yan , Zhu Jiang 
Published: December 2021

ObjectiveThe purpose of this study was to initially investigate the effect of previous antiangiogenic therapy (bevacizumab and endostatin) on the efficacy of anlotinib in patients with advanced or metastatic lung cancer (LC).MethodsWe retrospectively collected the clinical data of patients with LC treated with anlotinib and divided them into group A (treated with anlotinib after the failure of previous antiangiogenic drugs and group B (no prior use of antiangiogenic drugs). We used propensity score matching (PSM) for confounding factors between the groups. Progression-free survival (PFS) and overall survival (OS) were also recorded.ResultsA total of 160 patients were included in the analysis. The median OS in groups A and group B was 11.8 months and 16.1 months (P=0.120), whereas the median PFS was 3.1 months and 4.7 months (P=0.009), respectively. Moreover, the objective response rate (ORR) of the two groups was 9.6% and 10.4% (P=0.874), and the disease control rate (DCR) was 71.1% and 80.5% (P=0.165).After PSM (n=46), baseline characteristics were comparable between groups A and B. Furthermore, the median OS of the two groups was 14.6 months and 16.2 months (P=0.320), whereas the median PFS was 3.5 months and 4.5 months (P=0.040), respectively. Moreover, the ORR of the two groups were 13.0% and 10.9% (P=0.748), and the DCR were 78.3% and 82.6% (P=0.599), respectively.ConclusionsPrevious antiangiogenic treatments may affect the PFS of patients who receive anlotinib later, but it might not affect the patient’s ORR and OS.
The Association Between Sedentary Screen Time, Non-screen-based Sedentary Time, and Overweight in Chinese Preschool Children: A Cross-Sectional Study
Authors: Hu Rui , Zheng Hui , Lu Congchao 
Published: December 2021

Introduction: Less is known about the effects of the different domains of sedentary behaviors on healthy weight in young children. This cross-sectional study examined the association between sedentary screen time (SST), non-screen-based sedentary time (NSST), and overweight (and obesity) in Chinese preschoolers.Methods: Data were collected from the Physical Activity and Health in Tianjin Chinese Children study (PATH-CC), involving healthy children 3–6 years old and their families. Children's overweight status was classified according to the international (IOTF) childhood BMI cut-offs. SST and NSST were reported in minutes/day by parents using the leisure-time sedentary behaviors questionnaire. Logistic regression models adjusted by sex, age, socioeconomic status, outdoor play, and sleep duration were used.Results: In a total of 971 children (55.4% boys), 11.8% were overweight. Generally, children spent 1 h/day in SST and 1 h/day in NSST. Multiple models showed that children who spent more time in SST were more likely to be overweight [OR and 95% CI: 1.22 (1.03–1.45)]. No correlation between time spent on NSST and children with overweight was found (P &gt; 0.05).Conclusions: This study indicated that children who spent more time in SST were more likely to be overweight, but a null correlation between NSST and overweight was found. Longitudinal studies designed to identify associations between exposures to screen media and changes in metabolic parameters during a child's early years are needed.