bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophages-derived exosomal lncRNA LIFR-AS1 promotes osteosarcoma cell progression via miR-29a/NFIA axis
Authors: Zhang Hongliang , Yu Yiyang , Wang Jun , Han Yu , Ren Tingting , Huang Yi , Chen Chenglong , Huang Qingshan , Wang Wei , Niu Jianfang , Lou Jingbing , Guo Wei 
Published: April 2021

AbstractBackgroundOsteosarcoma (OS) is the most common primary malignant bone tumor in young people. Tumor-associated macrophages (TAMs) have been reported to play an important role in the development of osteosarcoma. However, the detailed molecular mechanisms remain largely unknown and need to be elucidated. Recently, exosomes have been reported as the crucial mediator between tumor cells and the tumor microenvironment. And a lot of lncRNAs have been reported to act as either oncogenes or tumor suppressors in osteosarcoma. In this research, we aim to explore the role of macrophages-derived exosomal lncRNA in osteosarcoma development and further elucidated the potential molecular mechanisms involved.MethodsTAMs were differentiated from human mononuclear cells THP-1, and a high-throughput microarray assay was used to analyze the dysregulated lncRNAs and miRNAs in osteosarcoma cells co-cultured with macrophages-derived exosomes. Western blot, qRT-PCR assays, and Dual-luciferase reporter assay were used to verify the interaction among LIFR-AS1, miR-29a, and NFIA. Cck-8, EdU, colony formation assay, wound-healing, and transwell assay were performed to explore the characterize the proliferation and metastasis ability of OS cells. And qPCR, Western blots, immunohistochemistry, and cell immunofluorescence were used to detect the expression of relative genes or proteins.ResultsIn this study, we found that THP-1-induced macrophage-derived exosomes could facilitate osteosarcoma cell progression both in vitro and in vivo. Then, the results of the high-throughput microarray assay showed that LIFR-AS1 was highly expressed and miR-29a was lowly expressed. Furthermore, LIFR-AS1 was identified as a miR-29a sponge, and NFIA was validated as a direct target of miR-29a. Functional assays demonstrated that knockdown of exosomal LIFR-AS1 could attenuate the promotion effects of macrophages-derived exosomes on osteosarcoma cell progression and miR-29a inhibition could reserve the effect of LIFR-AS1-knockdown exosomes. Correspondingly, NFIA-knockdown could partially reverse the tumor inhibition effect of miR-29a on osteosarcoma cells.ConclusionsTaken together, macrophages-derived exosomal lncRNA LIFR-AS1 can promote osteosarcoma cell proliferation, invasion, and restrain cell apoptosis via miR-29a/NFIA axis, which can act as a potential novel therapeutic target for osteosarcoma therapy.
Immunological significance of prognostic alternative splicing signature in hepatocellular carcinoma
Authors: Xu Qianhui , Xu Hao , Deng Rongshan , Li Nanjun , Mu Ruiqi , Qi Zhixuan , Shen Yunuo , Wang Zijie , Wen Jingchao , Zhao Jiaxin , Weng Di , Huang Wen 
Published: April 2021

Abstract
Background
Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality globally. Alternative splicing (AS) drives protein diversity, the imbalance of which might act an important factor in tumorigenesis. This study aimed to construct of AS-based prognostic signature and elucidate the role in tumor immune microenvironment (TIME) and immunotherapy in HCC.

Methods
Univariate Cox regression analysis was performed to determine the prognosis-related AS events and gene set enrichment analysis (GSEA) was employed for functional annotation, followed by the development of prognostic signatures using univariate Cox, LASSO and multivariate Cox regression. K-M survival analysis, proportional hazards model, and ROC curves were conducted to validate prognostic value. ESTIMATE R package, ssGSEA algorithm and CIBERSORT method and TIMER database exploration were performed to uncover the context of TIME in HCC. Quantitative real-time polymerase chain reaction was implemented to detect ZDHHC16 mRNA expression. Cytoscape software 3.8.0 were employed to visualize AS-splicing factors (SFs) regulatory networks.

Results
A total of 3294 AS events associated with survival of HCC patients were screened. Based on splicing subtypes, eight AS prognostic signature with robust prognostic predictive accuracy were constructed. Furthermore, quantitative prognostic nomogram was developed and exhibited robust validity in prognostic prediction. Besides, the consolidated signature was significantly correlated with TIME diversity and ICB-related genes. ZDHHC16 presented promising prospect as prognostic factor in HCC. Finally, the splicing regulatory network uncovered the potential functions of splicing factors (SFs).

Conclusion
Herein, exploration of AS patterns may provide novel and robust indicators (i.e., risk signature, prognostic nomogram, etc.,) for prognostic prediction of HCC. The AS-SF networks could open up new approach for investigation of potential regulatory mechanisms. And pivotal players of AS events in context of TIME and immunotherapy efficiency were revealed, contributing to clinical decision-making and personalized prognosis monitoring of HCC.
Efficacy and safety of dihydroartemisinin–piperaquine versus artemether–lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ugandan children: a systematic review and meta-analysis of randomized control trials
Authors: Assefa Dawit Getachew , Zeleke Eden Dagnachew , Bekele Delayehu , Tesfahunei Hanna Amanuel , Getachew Emnet , Joseph Michele , Manyazewal Tsegahun 
Published: April 2021

AbstractBackgroundThe emergence of artemisinin resistance in Southeast Asia andPlasmodium falciparum kelch13propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria. This is a critical concern in Uganda, where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum. The objective of this study was to compare the efficacy and safety of dihydroartemisinin–piperaquine (DHA–PQ) and artemether–lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Ugandan children.MethodsA search of PubMed and the Cochrane Central Register of Controlled Trials for retrieving randomized controlled trials comparing the efficacy and safety of DHA–PQ and AL for treatment of uncomplicated falciparum malaria in Ugandan children was done. The search was performed up to 31 August 2020. The data extracted from eligible studies and pooled as risk ratio (RR) with a 95% confidence interval (CI), using Rev Man Software (5.4). The protocol was registered in PROSPERO, ID: CRD42020182354.ResultsEleven trials were included in this review and two of them only included under safety outcome. Total 3798 participants were enrolled. The PCR unadjusted treatment failure was significantly lower with DHA–PQ at day 28 (RR 0.30, 95% CI 0.19–0.49; participants = 7863; studies = 5; I2 = 93%, low quality evidence) and at day 42 (RR 0.53, 95% CI 0.38–0.76; participants = 1618; studies = 4; I2 = 79%, moderate quality of evidence). The PCR adjusted treatment failure at day 42 was significantly lower with DHA–PQ treatment group (RR 0.45, 95% CI 0.28 to 0.72; participants = 1370; studies = 5, high quality of evidence), and it was below 5% in both arms at day 28 (moderate quality of evidence). AL showed a longer prophylactic effect on new infections which may last for up to 63 days (PCR-adjusted treatment failure: RR 2.04, 95% CI 1.13–3.70; participants = 1311; studies = 2, moderate quality of evidence). Compared to AL, DHA–PQ was associated with a slightly higher frequency of cough (RR 1.07, 95% CI 1.01 to 1.13; 2575 participants; six studies; high quality of evidence). In both treatment groups, the risk of recurrent parasitaemia due to possible recrudescence was less than 5% at day 28. The appearance of gametocyte between 29 and 42 days was also significantly lower in DHA–PQ than AL (RR 0.26, 95% CI 0.12 to 0.56; participants = 623; studies = 2; I2 = 0%).ConclusionCompared to AL, DHA–PQ appeared to reduce treatment failure and gametocyte carriage in Ugandan children. This may trigger DHA–PQ to become the first-line treatment option. Both treatments were safe and well-tolerated.
Asthmatic condition induced the activity of exosome secretory pathway in rat pulmonary tissues
Authors: Almohammai Asheed , Rahbarghazi Reza , Keyhanmanesh Rana , Rezaie Jafar , Ahmadi Mahdi 
Published: April 2021

Abstract
Background
The recent studies highlighted the critical role of exosomes in the regulation of inflammation. Here, we investigated the dynamic biogenesis of the exosomes in the rat model of asthma.

Results
Our finding showed an increase in the expression of IL-4 and the suppression of IL-10 in asthmatic lung tissues compared to the control samples (p < 0.05). Along with the promotion of IL-4, the protein level of TNF-α was induced, showing an active inflammatory status in OVA-sensitized rats. According to our data, the promotion of asthmatic responses increased exosome biogenesis indicated by increased CD63 levels and acetylcholine esterase activity compared to the normal condition (p < 0.05).

Conclusion
Data suggest that the stimulation of inflammatory response in asthmatic rats could simultaneously increase the paracrine activity of pulmonary cells via the exosome biogenesis. Exosome biogenesis may correlate with the inflammatory response.
Biomedical applications of 2D monoelemental materials formed by group VA and VIA: a concise review
Authors: Gao Ping , Xiao Yufen , YuliangWang  , Li Leijiao , Li Wenliang , Tao Wei 
Published: April 2021

AbstractThe development of two-dimensional (2D) monoelemental nanomaterials (Xenes) for biomedical applications has generated intensive interest over these years. In this paper, the biomedical applications using Xene-based 2D nanomaterials formed by group VA (e.g., BP, As, Sb, Bi) and VIA (e.g., Se, Te) are elaborated. These 2D Xene-based theranostic nanoplatforms confer some advantages over conventional nanoparticle-based systems, including better photothermal conversion, excellent electrical conductivity, and large surface area. Their versatile and remarkable features allow their implementation for bioimaging and theranostic purposes. This concise review is focused on the current developments in 2D Xenes formed by Group VA and VIA, covering the synthetic methods and various biomedical applications. Lastly, the challenges and future perspectives of 2D Xenes are provided to help us better exploit their excellent performance and use them in practice.
Lessons from the pandemic on the value of research infrastructure
Authors: Roope Laurence S. J. , Candio Paolo , Kiparoglou Vasiliki , McShane Helen , Duch Raymond , Clarke Philip M. 
Published: April 2021

AbstractThe COVID-19 pandemic has shed a spotlight on the resilience of healthcare systems, and their ability to cope efficiently and effectively with unexpected crises. If we are to learn one economic lesson from the pandemic, arguably it is the perils of an overfocus on short-term allocative efficiency at the price of lack of capacity to deal with uncertain future challenges. In normal times, building spare capacity with ‘option value’ into health systems may seem inefficient, the costs potentially exceeding the benefits. Yet the fatal weakness of not doing so is that this can leave health systems highly constrained when dealing with unexpected, but ultimately inevitable, shocks—such as the COVID-19 pandemic. In this article, we argue that the pandemic has highlighted the potentially enormous option value of biomedical research infrastructure. We illustrate this with reference to COVID-19 response work supported by the United Kingdom National Institute for Health Research Oxford Biomedical Research Centre. As the world deals with the fallout from the most serious economic crisis since the Great Depression, pressure will soon come to review government expenditure, including research funding. Developing a framework to fully account for option value, and understanding the public appetite to pay for it, should allow us to be better prepared for the next emerging problem.
Perspectives of individuals with chronic spinal cord injury following novel balance training involving functional electrical stimulation with visual feedback: a qualitative exploratory study
Authors: Houston David J. , Unger Janelle , Lee Jae W. , Masani Kei , Musselman Kristin E. 
Published: April 2021

Abstract
Background
Individuals with an incomplete spinal cord injury (iSCI) are highly susceptible to falls during periods of walking or standing. We recently reported the findings of a novel intervention combining functional electrical stimulation with visual feedback balance training (FES + VFBT) on standing balance abilities among five individuals with motor iSCI. However, the previous publication did not report the perceived impact of the intervention on the participants’ lives. In this report, the experiences of these five individuals with incomplete spinal cord injury (iSCI) who had recently completed the four-week balance training program are described.

Methods
Five individuals with a motor iSCI took part in this study. Each individual was at least 12 months post-injury, capable of unassisted standing for 60 s and had a Berg Balance Scale Score < 46. Participants completed twelve sessions of a novel balance intervention combining closed-loop functional electrical stimulation with visual feedback balance training (FES + VFBT). Participants received visual feedback regarding their centre of pressure position as they completed balance-training exercises while FES was applied to the ankle plantarflexors and dorsiflexors bilaterally. Semi-structured interviews were conducted after completion of the balance training intervention and eight-weeks post-training to understand participant’s experiences. Categories and themes were derived from the transcripts using conventional content analysis.

Results
Three themes were identified from the collected transcripts: (1) Perceived benefits across International Classification of Functioning, Disability and Health levels; (2) Change in perceived fall risk and confidence; (3) Motivation to keep going.

Conclusions
Participation in the FES + VFBT program resulted in perceived benefits that led to meaningful improvements in activities of daily living. Following completion of the training, individuals felt they still had the capacity to improve. Individuals felt they had increased their balance confidence, while a few participants also reported a decrease in their risk of falling. The inclusion of qualitative inquiry allows for the evaluation of the meaningfulness of an intervention and its perceived impact on the lives of the participants.
Trial registration: NCT04262414 (retrospectively registered February 10, 2020)
Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases
Authors: Eide Per Kristian , Valnes Lars Magnus , Lindstrøm Erika Kristina , Mardal Kent-Andre , Ringstad Geir 
Published: April 2021

Abstract
Background
Several central nervous system diseases are associated with disturbed cerebrospinal fluid (CSF) flow patterns and have typically been characterized in vivo by phase-contrast magnetic resonance imaging (MRI). This technique is, however, limited by its applicability in space and time. Phase-contrast MRI has yet to be compared directly with CSF tracer enhanced imaging, which can be considered gold standard for assessing long-term CSF flow dynamics within the intracranial compartment.

Methods
Here, we studied patients with various CSF disorders and compared MRI biomarkers of CSF space anatomy and phase-contrast MRI at level of the aqueduct and cranio-cervical junction with dynamic intrathecal contrast-enhanced MRI using the contrast agent gadobutrol as CSF tracer. Tracer enrichment of cerebral ventricles was graded 0–4 by visual assessment. An intracranial pressure (ICP) score was used as surrogate marker of intracranial compliance.

Results
The study included 94 patients and disclosed marked variation of CSF flow measures across disease categories. The grade of supra-aqueductal reflux of tracer varied, with strong reflux (grades 3–4) in half of patients. Ventricular tracer reflux correlated with stroke volume and aqueductal CSF pressure gradient. CSF flow in the cerebral aqueduct was retrograde (from 4th to 3rd ventricle) in one third of patients, with estimated CSF net flow volume about 1.0 L/24 h. In the cranio-cervical junction, net flow was cranially directed in 78% patients, with estimated CSF net flow volume about 4.7 L/24 h.

Conclusions
The present observations provide in vivo quantitative evidence for substantial variation in direction and magnitude of CSF flow, with re-direction of aqueductal flow in communicating hydrocephalus, and significant extra-cranial CSF production. The grading of ventricular reflux of tracer shows promise as a clinical useful method to assess CSF flow pattern disturbances in patients.

Graphic abstract
Cochlea sparing optimized radiotherapy for nasopharyngeal carcinoma
Authors: Lamaj Enkelejda , Vu Erwin , van Timmeren Janita E. , Leonardi Chiara , Marc Louise , Pytko Izabela , Guckenberger Matthias , Balermpas Panagiotis 
Published: April 2021

Abstract
Background
Definitive chemoradiotherapy (CRT) is standard of care for nasopharyngeal carcinoma. Due to the tumor localization and concomitant platinum-based chemotherapy, hearing impairment is a frequent complication, without defined dose-threshold. In this study, we aimed to achieve the maximum possible cochleae sparing.

Materials and methods
Treatment plans of 20 patients, treated with CRT (6 IMRT and 14 VMAT) based on the QUANTEC organs-at-risk constraints were investigated. The cochleae were re-delineated independently by two radiation oncologists, whereas target volumes and other organs at risk (OARs) were not changed. The initial plans, aiming to a mean cochlea dose < 45 Gy, were re-optimized with VMAT, using 2–2.5 arcs without compromising the dose coverage of the target volume. Mean cochlea dose, PTV coverage, Homogeneity Index, Conformity Index and dose to other OAR were compared to the reference plans. Wilcoxon signed-rank test was used to evaluate differences, a p value < 0.05 was considered significant.

Results
The re-optimized plans achieved a statistically significant lower dose for both cochleae (median dose for left and right 14.97 Gy and 18.47 Gy vs. 24.09 Gy and 26.05 Gy respectively, p < 0.001) compared to the reference plans, without compromising other plan quality parameters. The median NTCP for tinnitus of the most exposed sites was 11.3% (range 3.52–91.1%) for the original plans, compared to 4.60% (range 1.46–90.1%) for the re-optimized plans (p < 0.001). For hearing loss, the median NTCP of the most exposed sites could be improved from 0.03% (range 0–99.0%) to 0.00% (range 0–98.5%, p < 0.001).

Conclusions
A significantly improved cochlea sparing beyond current QUANTEC constraints is feasible without compromising the PTV dose coverage in nasopharyngeal carcinoma patients treated with VMAT. As there appears to be no threshold for hearing toxicity after CRT, this should be considered for future treatment planning.
Clinical and echocardiographic trends in percutaneous balloon mitral valvuloplasty
Authors: Koren Ofir , Israeli Asaf , Rozner Ehud , Darawshy Nassem , Turgeman Yoav 
Published: April 2021

Abstract
Background
The prevalence of Rheumatic Mitral Stenosis (MS) has significantly changed over the last decades. We intend to examine patient demographics, Echocardiographic characteristics, procedural success rates, and complications throughout 30-years.

Methods
We conducted a single-center descriptive observational study. The study population consists of patients undergone percutaneous balloon mitral valvuloplasty (PBMV) at Emek Medical Center in Israel from January 1990 to May 2019.

Results
Four hundred seventeen patients underwent PBMV during the study period and were eligible for the study. Age did not change significantly over time (p = 0.09). The prevalence of Male and patients who were smoking and had multiple comorbidities such as hypertension, dyslipidemia, ischemic heart disease, and chronic kidney disease became increases over time (p = 0.02, p = 0.02, p = 0.001, p = 0.01, p = 0.02, and p = 0.001, respectively). Wilkins score and all its components increased over time, and the total score was higher in females (p = 0.01). Seventy-nine (18.9%) patients had complications. The rate of complications did not change over decades. Patients with Wilkins score > 8, post-procedural MR of ≥2, and post-procedural MVA < 1.5 had the highest risk for the need of Mitral valve replacement (MVR) surgery in 2 years following PBMV (3.64, 4.03, 2.44, respectively, CI 95%, p < .0001 for all). The median time in these patients was 630 days compared to 4–5 years in the entire population. Patients with Post-procedural MR of ≥2 and post-procedural MVA < 1.5 had ten times risk for developing heart failure (HR 9.07 and 10.06, respectively, CI 95%, P < .0001).

Conclusion
Our research reveals trends over time in patients’ characteristics and echocardiographic features. Our study population consists of more male patients with multiple comorbidities and more complex and calcified valvular structures in the last decade. Wilkins score > 8, post-procedural MR of ≥2, and post-procedural MVA < 1.5 cm2 were in-depended predictors for the time for surgery and heart failure hospitalization.
The role of the circadian clock in cancer hallmark acquisition and immune-based cancer therapeutics
Authors: Cash Elizabeth , Sephton Sandra , Woolley Cassandra , Elbehi Attia M. , R. I. Anu , Ekine-Afolabi Bene , Kok Victor C. 
Published: April 2021

AbstractThe circadian system temporally regulates physiology to maintain homeostasis. Co-opting and disrupting circadian signals appear to be distinct attributes that are functionally important for the development of a tumor and can enable or give rise to the hallmarks that tumors use to facilitate their initiation, growth and progression. Because circadian signals are also strong regulators of immune cell proliferation, trafficking and exhaustion states, they play a role in how tumors respond to immune-based cancer therapeutics. While immuno-oncology has heralded a paradigm shift in cancer therapeutics, greater accuracy is needed to increase our capability of predicting who will respond favorably to, or who is likely to experience the troubling adverse effects of, immunotherapy. Insights into circadian signals may further refine our understanding of biological determinants of response and help answer the fundamental question of whether certain perturbations in circadian signals interfere with the activity of immune checkpoint inhibitors. Here we review the body of literature highlighting circadian disruption as a cancer promoter and synthesize the burgeoning evidence suggesting circadian signals play a role in how tumors respond to immune-based anti-cancer therapeutics. The goal is to develop a framework to advance our understanding of the relationships between circadian markers, cancer biology, and immunotherapeutics. Bolstered by this new understanding, these relationships may then be pursued in future clinical studies to improve our ability to predict which patients will respond favorably to, and avoid the adverse effects of, traditional and immune-based cancer therapeutics.