bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter-study and time-dependent variability of metabolite abundance in cultured red blood cells
Authors: Tewari Shivendra G. , Rajaram Krithika , Swift Russell P. , Kwan Bobby , Reifman Jaques , Prigge Sean T. , Wallqvist Anders 
Published: July 2021

Abstract
Background
Cultured human red blood cells (RBCs) provide a powerful ex vivo assay platform to study blood-stage malaria infection and propagation. In recent years, high-resolution metabolomic methods have quantified hundreds of metabolites from parasite-infected RBC cultures under a variety of perturbations. In this context, the corresponding control samples of the uninfected culture systems can also be used to examine the effects of these perturbations on RBC metabolism itself and their dependence on blood donors (inter-study variations).

Methods
Time-course datasets from five independent studies were generated and analysed, maintaining uninfected RBCs (uRBC) at 2% haematocrit for 48 h under conditions originally designed for parasite cultures. Using identical experimental protocols, quadruplicate samples were collected at six time points, and global metabolomics were employed on the pellet fraction of the uRBC cultures. In total, ~ 500 metabolites were examined across each dataset to quantify inter-study variability in RBC metabolism, and metabolic network modelling augmented the analyses to characterize the metabolic state and fluxes of the RBCs.

Results
To minimize inter-study variations unrelated to RBC metabolism, an internal standard metabolite (phosphatidylethanolamine C18:0/20:4) was identified with minimal variation in abundance over time and across all the samples of each dataset to normalize the data. Although the bulk of the normalized data showed a high degree of inter-study consistency, changes and variations in metabolite levels from individual donors were noted. Thus, a total of 24 metabolites were associated with significant variation in the 48-h culture time window, with the largest variations involving metabolites in glycolysis and synthesis of glutathione. Metabolic network analysis was used to identify the production of superoxide radicals in cultured RBCs as countered by the activity of glutathione oxidoreductase and synthesis of reducing equivalents via the pentose phosphate pathway. Peptide degradation occurred at a rate that is comparable with central carbon fluxes, consistent with active degradation of methaemoglobin, processes also commonly associated with storage lesions in RBCs.

Conclusions
The bulk of the data showed high inter-study consistency. The collected data, quantification of an expected abundance variation of RBC metabolites, and characterization of a subset of highly variable metabolites in the RBCs will help in identifying non-specific changes in metabolic abundances that may obscure accurate metabolomic profiling of Plasmodium falciparum and other blood-borne pathogens.
Associations of park access, park use and physical activity in parks with wellbeing in an Asian urban environment: a cross-sectional study
Authors: Petrunoff Nicholas A. , Yi Ng Xian , Dickens Borame , Sia Angelia , Koo Joel , Cook Alex R. , Lin Wee Hwee , Ying Lu , Hsing Ann W. , van Dam Rob M. , Müller-Riemenschneider Falk 
Published: July 2021

Abstract
Background
Relationships between park access, park use, and wellbeing remain poorly understood. The objectives of this study were to investigate: (1) perceived and objective park access in relation to park use and physical activity in parks; and; (2) perceived and objective park access, park use and physical activity in parks and their associations with wellbeing.

Methods
An interviewer-assisted survey collected data on perceived time to walk to parks, park use time, park physical activity time and wellbeing (using a scale containing nine domains) amongst adult participants of the Singapore Multi-Ethnic Cohort. Geospatial maps of parks and the “walkable” street networks were created for the city-state of Singapore to objectively determine distances to accessible points on park boundaries. Multiple linear regression models estimated the importance of park access to park use and associations of park access and park use with wellbeing, adjusting for potential confounders.

Results
Participants’ (n = 3435) average age was 48.8 years (SD, 12.8), 44.8% were male and 72.6% were of Chinese ethnicity. Better perceived but not true park access was significantly associated with greater park use. Park access (perceived or true) was not associated with physical activity time in parks. Greater participant park time and physical activity time in parks were associated with higher wellbeing scores (p < 0.001). The differences in wellbeing scores between the reference groups, who spent negligible time in parks, and the highest quartiles of time in parks (10.8 h/month) and physical activity in parks (8.3 h/month) were 3.2 (95% CI 2.1–4.4) and 4.2 (95% CI 4.1–6.3) points out of 100 respectively. These associations were similar for most domains of wellbeing, with clear dose-response relationships.

Conclusions
While perceived park access was strongly associated with park use and well-being, true park access was not, and neither park access measure was associated with park physical activity. Future studies could investigate the influence of park attributes on park use, physical activity in parks and wellbeing. The consistent associations of park use and particularly physical activity in parks with wellbeing suggest that promoting park use, and especially physical activity in parks, is a promising strategy for improving wellbeing in urban settings.
Is there a relationship between psoriasis and hepatitis C? A meta-analysis and bioinformatics investigation
Authors: Liu Yong , Cui Sheng Nan , Duan Meng Yao , Dou Zhi Li , Li Yi Zhen , Liu Yi Xing , Xia Ye , Zhang Jia Wei , Yan Xiao Ning , Han Dong Ran 
Published: July 2021

AbstractBackgroundThe relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.MethodsWe conducted a systematic review of the case–control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein–protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis.ResultsWe included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case–control). The case–control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17–2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine–cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis.ConclusionPatients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.
Effectiveness of bazedoxifene in preventing glucocorticoid-induced bone loss in rheumatoid arthritis patients
Authors: Cho Soo-Kyung , Kim Hyoungyoung , Lee Jiyoung , Nam Eunwoo , Lee Seunghun , Choi Yun Young , Sung Yoon-Kyoung 
Published: July 2021

Abstract
Objective
To evaluate the effectiveness of bazedoxifene in preventing bone loss in patients with rheumatoid arthritis (RA) receiving low-dose glucocorticoids (GCs).

Methods
In this randomized, controlled, open-label study, we assigned postmenopausal women with osteopenia who had been receiving low-dose GCs for RA to two groups: a group receiving bazedoxifene (20 mg/day) with elemental calcium 1200 mg and vitamin D 800 IU daily (bazedoxifene group) and a group receiving the same doses of calcium and vitamin D only (control group). As primary outcome, bone mineral density (BMD) change in the lumbar spine (L-spine) from baseline to 48 weeks was assessed. Changes in BMD in the femur, trabecular bone score, bone turnover markers, and development of fracture were assessed as secondary outcomes. For intention-to-treat analysis, 20 completed data sets were created by applying multiple imputations by chained equations.

Results
A total of 114 patients (57 patients in each group) were recruited. A significant increase in L-spine BMD (0.015 g/cm2, P = 0.007) was observed in the bazedoxifene group, and the increase was significantly higher than in the control group (0.013, 95% CI 0.0003–0.026, P = 0.047). Reductions in bone turnover markers in the bazedoxifene group were significantly greater than in the control group. Only one fracture was observed in the bazedoxifene group, while four fractures developed in the control group.

Conclusion
In postmenopausal patients with RA receiving low-dose GCs, bazedoxifene improved BMD and reduced bone turnover markers. However, the change in BMD did not exceed the least significant change.

Trial registration
ClinicalTrials.gov, NCT02602704.
Mean value of B-mode optic nerve sheath diameter as an indicator of increased intracranial pressure: a systematic review and meta-analysis
Authors: Montorfano Lisandro , Yu Qian , Bordes Stephen J. , Sivanushanthan Shankarapryan , Rosenthal Raul J. , Montorfano Miguel 
Published: July 2021

Abstract
Objectives
Timely diagnosis and treatment of increased intracranial pressure can decrease morbidity and prevent mortality. The present meta-analysis aims to determine the mean value of the ONSD measured in patients with various elevated ICP etiologies under different clinical settings, as well as comparing the value of ONSD between patients with and without elevated ICP.

Methods
This meta-analysis complied with the Preferred Reporting Items for Systematic Reviews and Meta-analysis Statement8. PubMed, Embase, and Cochrane Library were searched to identify ONSD measured by US for patients with increased ICP from establishment to October 2020.

Results
A total of 779 patients with elevated ICP among 22 studies were included in the present meta-analysis. Studies were published between 2003 and 2020. Eighteen were comparative (18/22, 81.8%), and four were single-armed study (4/22, 18.2%). Twenty were prospective studies (20/22, 90.9%). There was moderate-to-high heterogeneity based on the prediction ellipse area and variance logit of sensitivity and specificity.

Conclusions
The mean value of the ONSD among patients diagnosed with increased ICP was 5.82 mm (95% CI 5.58–6.06 mm). Variations were observed based on etiology of intracranial hypertension, clinical settings where ONSD was measured, and standards for diagnosing intracranial hypertension. The US-ONSD among patient with elevated ICP was significantly higher than the normal control. Although a cut-off value is not clearly determined, these mean values can be implemented to evaluate the sensitivity and specificity of US-ONSD in diagnosing intracranial hypertension in future studies.
Clinical value of 3'-deoxy-3'-[18F]fluorothymidine-positron emission tomography for diagnosis, staging and assessing therapy response in lung cancer
Authors: Alwadani Bandar , Dall’Angelo Sergio , Fleming Ian N. 
Published: July 2021

AbstractLung cancer has the highest mortality rate of any tumour type. The main driver of lung tumour growth and development is uncontrolled cellular proliferation. Poor patient outcomes are partly the result of the limited range of effective anti-cancer therapies available and partly due to the limited accuracy of biomarkers to report on cell proliferation rates in patients. Accordingly, accurate methods of diagnosing, staging and assessing response to therapy are crucial to improve patient outcomes. One effective way of assessing cell proliferation is to employ non-invasive evaluation using 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography [18F]FLT-PET. [18F]FLT, unlike the most commonly used PET tracer [18F]fluorodeoxyglucose ([18F]FDG), can specifically report on cell proliferation and does not accumulate in inflammatory cells. Therefore, this radiotracer could exhibit higher specificity in diagnosis and staging, along with more accurate monitoring of therapy response at early stages in the treatment cycle. This review summarises and evaluates published studies on the clinical use of [18F]FLT to diagnose, stage and assess response to therapy in lung cancer.
A critical review on altmetrics: can we measure the social impact factor?
Authors: García-Villar Cristina 
Published: July 2021

AbstractAltmetrics measure the digital attention received by a research output. They allow us to gauge the immediate social impact of an article by taking real-time measurements of how it circulates in the Internet. While there are several companies offering attention scores, the most extensive are Altmetric.com (Altmetric Attention Score—AAS) and Plum X (Plum Print). As this is an emerging topic, many medical specialities have tried to establish if there is a relationship between an article’s altmetric data and the citations it subsequently receives. The results have varied depending on the research field. In radiology, the social network most used is Twitter and the subspeciality with the highest AAS is neuroimaging. This article will review the process involved from the start when an article is published through to finally obtaining its altmetric score. It will also address the relationship between altmetrics and more traditional approaches focusing on citations in radiology and will discuss the advantages and limitations of these new impact indicators.
Appearance of the levator ani muscle subdivisions on 3D transperineal ultrasound
Authors: Manzini Claudia , van den Noort Frieda , Grob Anique T. M. , Withagen Mariëlla I. J. , Slump Cornelis H. , van der Vaart C. Huub 
Published: July 2021

Abstract
Background
The levator ani muscle (LAM) consists of different subdivisions, which play a specific role in the pelvic floor mechanics. The aim of this study is to identify and describe the appearance of these subdivisions on 3-Dimensional (3D) transperineal ultrasound (TPUS). To do so, a study designed in three phases was performed in which twenty 3D TPUS scans of vaginally nulliparous women were assessed. The first phase was aimed at getting acquainted with the anatomy of the LAM subdivisions and its appearance on TPUS: relevant literature was consulted, and the TPUS scan of one patient was analyzed to identify the puborectal, iliococcygeal, puboperineal, pubovaginal, and puboanal muscle. In the second phase, the five LAM subdivisions and the pubic bone and external sphincter, used as reference structures, were manually segmented in volume data obtained from five nulliparous women at rest. In the third phase, intra- and inter-observer reproducibility were assessed on twenty TPUS scans by measuring the Dice Similarity Index (DSI).

Results
The mean inter-observer and median intra-observer DSI values (with interquartile range) were: puborectal 0.83 (0.13)/0.83 (0.10), puboanal 0.70 (0.16)/0.79 (0.09), iliococcygeal 0.73 (0.14)/0.79 (0.10), puboperineal 0.63 (0.25)/0.75 (0.22), pubovaginal muscle 0.62 (0.22)/0.71 (0.16), and the external sphincter 0.81 (0.12)/0.89 (0.03).

Conclusion
Our results show that the LAM subdivisions of nulliparous women can be reproducibly identified on 3D TPUS data.
High-efficiency c-Myc-mediated induction of functional hepatoblasts from the human umbilical cord mesenchymal stem cells
Authors: Deng Jie , Luo Kai , Xu Pengchao , Jiang Qingyuan , Wang Yuan , Yao Yunqi , Chen Xiaolei , Cheng Fuyi , Xie Dan , Deng Hongxin 
Published: July 2021

Abstract
Background
Direct reprogramming of human fibroblasts to hepatocyte-like cells was proposed to generate large-scale functional hepatocytes demanded by liver tissue engineering. However, the difficulty in obtaining large quantities of human fibroblasts greatly restricted the extensive implementation of this approach. Meanwhile, human umbilical cord mesenchymal stem cells (HUMSCs) are the preferred cell source for HLCs with the advantages of limited ethical concerns, easy accessibility, and propagation in vitro. However, no direct reprogramming protocol for converting HUMSCs to hepatoblast-like cells (HLCs) has been reported.

Methods
HLCs were successfully generated from HUMSCs by forced expression of FOXA3, HNF1A, and HNF4A (collectively as 3TFs) and c-Myc. In vitro and in vivo functional experiments were conducted to demonstrate the hepatic phenotype, characterization, and function of HUMSC-derived HLCs (HUMSC-iHeps). ChIP-seq and RNA-seq were integrated to reveal the potential molecular mechanisms underlying c-Myc-mediated reprogramming.

Results
We showed that c-Myc greatly improved the trans-differentiation efficiency for HLCs from HUMSCs, which remained highly efficient in reprogramming fibroblasts into HLCs, suggesting c-Myc could promote direct reprogramming and its potentially widespread applicability for generating large amounts of HLCs in vitro. Mice transplantation experiments further confirmed the therapeutic potential of HUMSC-iHeps by liver function restoration and survival prolongation. Besides, in vivo safety assessment demonstrated the low risk of the tumorigenic potential of HUMSC-iHeps. We found that c-Myc functioned predominantly at an early phase of reprogramming, and we further unraveled the regulatory network altered by c-Myc.

Conclusions
c-Myc enhanced reprogramming efficiency of HLCs from HUMSCs. A large scale of functional HLCs generated more conveniently from HUMSCs could benefit biomedical studies and applications of liver diseases.
Systemic therapy of MSCs in bone regeneration: a systematic review and meta-analysis
Authors: Fu Jingfei , Wang Yanxue , Jiang Yiyang , Du Juan , Xu Junji , Liu Yi 
Published: July 2021

Abstract
Objectives
Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies.

Methods
The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases.

Results
Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV).

Conclusion
This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments.
Mesenchymal stem cells alleviate idiopathic pneumonia syndrome by modulating T cell function through CCR2-CCL2 axis
Authors: Cao Min , Liu Huihui , Dong Yujun , Liu Wei , Yu Zhengyu , Wang Qingya , Wang Qingyun , Liang Zeying , Li Yuan , Ren Hanyun 
Published: July 2021

Abstract
Background
Idiopathic pneumonia syndrome (IPS) is a non-infectious fatal complication characterized by a massive infiltration of leukocytes in lungs and diffuse pulmonary injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Conventional immunosuppressive treatments for IPS have poor therapeutic effects. Safe and effective treatments are not yet available and under explorations. Our previous study demonstrated that mesenchymal stem cells (MSCs) can alleviate IPS, but the mechanisms remain unclear.

Methods
Co-cultured pre-activated T cells and MSCs in vitro to observe the changes in the CCR2-CCL2 axis. By establishing an IPS mouse model and administering MSCs to further verify the results of in vitro experiments.

Results
Co-culture of pre-activated T cells with MSCs in vitro modulated the CCR2-CCL2 axis, resulting in quiescent T cells and polarization toward CCR2+CD4+ T cell subsets. Blocking CCR2-CCL2 interaction abolished the immunoregulatory effect of MSCs, leading to re-activation of T cells and partial reversion of polarizing toward CCR2+CD4+ T cells. In IPS mouse model, application of MSCs prolonged the survival and reduced the pathological damage and T cell infiltration into lung tissue. Activation of CCR2-CCL2 axis and production of CCR2+CD4+ T cells were observed in the lungs treated with MSCs. The prophylactic effect of MSCs on IPS was significantly attenuated by the administration of CCR2 or CCL2 antagonist in MSC-treated mice.

Conclusions
We demonstrated an important role of CCR2-CCL2 axis in modulating T cell function which is one of the mechanisms of the prophylactic effect of MSCs on IPS.
Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury
Authors: Yu Lu , Liu Siying , Wang Chen , Zhang Chuanyu , Wen Yajie , Zhang Kaiyue , Chen Shang , Huang Haoyan , Liu Yue , Wu Lingling , Han Zhongchao , Chen Xiangmei , Li Zongjin , Liu Na 
Published: July 2021

Abstract
Background
Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear.

Methods
In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro.

Results
We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells.

Conclusions
ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.