bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer
Authors: Liu Yaqian , Pan Bo , Qu Weikun , Cao Yilong , Li Jun , Zhao Haidong 
Published: February 2021

Abstract
Background: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.Methods: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. We also showed that knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases. Results: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, we identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC. Conclusion: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.
Development and evaluation of a new&nbsp;Plasmodium falciparum&nbsp;3D7 blood stage malaria cell bank for use in malaria volunteer infection studies
Authors: Woolley Stephen Derek , Fernandez Melissa , Rebelo Maria , Llewellyn Stacey , Marquart Louise , Amante Fiona , Jennings Helen , Webster Rebecca , Trenholme Katharine , Chalon Stephan , Moehrle Joerg , McCarthy James , Barber Bridget 
Published: February 2021

Abstract
Background New anti-malarial therapeutics are required to counter the threat of increasing drug resistance. Malaria volunteer infection studies (VIS), particularly the induced blood stage malaria (IBSM) model, play a key role in accelerating anti-malarial drug development. Supply of the reference 3D7-V2 Plasmodium falciparum malaria cell bank (MCB) is limited. This study aimed to develop a new MCB, and compare the safety and infectivity of this MCB with the existing 3D7-V2 MCB, in a VIS. A second bank (3D7-V1) developed in 1995 was also evaluated.Methods The 3D7-V2 MCB was expanded in vitro using a bioreactor to produce a new MCB designated 3D7-MBE-008. This bank and 3D7-V1 were then evaluated using the IBSM model, where healthy participants were intravenously inoculated with blood-stage parasites. Participants were treated with artemether-lumefantrine when parasitaemia or clinical thresholds were reached. Safety, infectivity and parasite growth and clearance were evaluated. Results The in vitro expansion of 3D7-V2 produced 200 vials of the 3D7-MBE-008 MCB, with a parasitaemia of 4.3%. This compares to 0.1% in the existing 3D7-V2 MCB, and <0.01% in the 3D7-V1 MCB. All four participants (two per MCB) developed detectable P. falciparum infection after inoculation with approximately 2800 parasites. For the 3D7-MBE-008 MCB, the parasite multiplication rate of 48 hours (PMR48) using non-linear mixed effects modelling was 34.6 (95% CI: 18.5 – 64.6), similar to the parental 3D7-V2 line; parasitaemia in both participants exceeded 10,000/mL by day 8. Growth of the 3D7-V1 was slower (PMR48 of 11.5 [95% CI: 8.5 – 15.6]), with parasitaemia exceeding 10,000 parasites/mL on days 10 and 8.5. Rapid parasite clearance followed artemether-lumefantrine treatment in all four participants, with clearance half-lives of 4.01 and 4.06 (weighted mean 4.04 [95% CI: 3.61 – 4.57]) hours for 3D7-MBE-008 and 4.11 and 4.52 (weighted mean 4.31 [95% CI: 4.16 – 4.47]) hours for 3D7-V1. A total of 59 adverse events occurred; most were of mild severity with three being severe in the 3D7-MBE-008 study. Conclusion The safety, growth and clearance profiles of the expanded 3D7-MBE-008 MCB closely resemble that of its parent, indicating its suitability for future studies. Trial Registration Australian New Zealand Clinical Trials registry numbers:P3487 (3D7-V1): ACTRN12619001085167P3491 (3D7-MBE-008): ACTRN12619001079134
An integrated analysis of spatial access to the three-tier healthcare delivery system in China: A case study of Hainan Island
Authors: Wang Xiuli , Seyler Barnabas , Han Wei , Pan Jay 
Published: February 2021

Abstract
Background: Access to healthcare is critical for the implementation of Universal Health Coverage. With the development of healthcare insurance systems around the world, spatial impedance to healthcare institutions has attracted increasing attention. However, most spatial access methodologies have been developed in Western countries, whose healthcare systems are different from those in Low- and Middle-Income Countries (LMICs).Methods: Hainan Island was taken as an example to explore the utilization of modern spatial access techniques under China’s specialized Three-Tier Health Care Delivery System. Healthcare institutions were first classified according to the three tiers. Then shortest travel time was calculated for each institution’s tier, overlapped to identify eight types of multilevel healthcare access zones. Spatial access to doctors based on the Enhanced Two-Step Floating Catchment Area Method was also calculated.Results: On Hainan Island, about 90% of the population lived within a 60-minute service range for Tier 3 (hospital) healthcare institutions, 80% lived within 30 minutes of Tier 2 (health centers), and 75% lived within 15 minutes of Tier 1 (clinics). Based on local policy, 76.36% of the population living in 48.52% of the area were able to receive timely services at all tiers of healthcare institutions. The weighted average access to doctors was 2.31 per thousand residents, but the regional disparity was large, with 64.66% being contributed by Tier 3 healthcare institutions.Conclusion: Spatial access to healthcare institutions on Hainan Island was generally good according to travel time and general abundance of doctors, but inequity between regions and imbalance between different healthcare institution tiers exist. Primary healthcare institutions, especially in Tier 2, should be strengthened.
Substitution of ROTEM FIBTEM A5 for A10 in Trauma: An Observational Study Building a Case for More Rapid Analysis of Coagulopathy
Authors: Blayney Alexander , McCullough James P. A. , Wake Elizabeth , Walters Kerin , Campbell Don , Ho Debbie , Chan Erick , Chalasani Aashish , Winearls James 
Published: February 2021

Abstract
Purpose Rotational thromboelastometry (ROTEM®) allows guided blood product resuscitation to correct trauma induced coagulopathy in bleeding trauma patients. FIBTEM amplitude at 10 minutes (A10) has been widely used to identify hypofibrinogenaemia; locally a threshold of < 11 mm has guided fibrinogen replacement. Amplitude at 5 minutes (A5) carries an inherent time advantage. The primary aim was to explore the relationship between FIBTEM A5 and A10 in a trauma. Secondary aim was to investigate the use of A5 as a surrogate for A10 within a fibrinogen-replacement algorithm.Methods Retrospective observational cohort study of arrival ROTEM results from 1539 consecutive trauma patients at a Level 1 trauma centre in Australia. Consistency of agreement between FIBTEM A5 and A10 was assessed. A new fibrinogen replacement threshold was developed for A5 using the A5 – A10 bias; this was clinically compared to the existing A10 threshold.Results FIBTEM A5 displayed excellent consistency of agreement with A10. Intraclass correlation coefficient = 0.972 (95% confidence interval [CI] 0.969 – 0.974). Bias of A5 to A10 was -1.49 (95% CI 1.43 -1.56) mm. 19.34% patients met the original local threshold of A10 < 11 mm; 19.28% patients met the new, bias-adjusted threshold of A5 < 10 mm.Conclusions ROTEM FIBTEM A5 reliably predicts A10 in trauma. This further validates use of the A5 result over A10 allowing faster decision-making in time-critical resuscitation of trauma patients. A modification of -1 to the A10 threshold might be appropriate for use with the A5 value in trauma patients.
Elevation of miR-302b prevents multiple myeloma cell growth and bone destruction by blocking DKK1 secretion
Authors: Wu Zheyu , Zhang Yufeng , Yang Zhiqiang , Zhu Yufan , Xie Yuanlong , Zhou Fuling , Cai Lin 
Published: February 2021

Abstract
Background: Myeloma bone disease (MBD) is a severe complication of multiple myeloma (MM) mainly due to an imbalance between enhanced osteoclast activity and reduced osteoblast function. Previous studies have demonstrated that miRNAs play a vital role in the osteogenic differentiation of mesenchymal stromal cells (MSCs) in MM. However, the value of miR‑302b in MBD remains to be further elucidated. The aim of this study was to explore the role of miR‑302b in the regulation of MBD osteogenic differentiation and evaluate the potential of a new therapeutic strategy for the clinical treatment of MBD.Method: Our previous research demonstrated that MiR-302b belonged to the miR-302 cluster and could inhibit tumor growth and osteolysis in an orthotopic osteosarcoma xenograft tumor mouse model. In this study, we first transfected miR-302b mimics, miR-302b inhibitor, and miR-302b NC into MM1.S and RPMI8226 MM cells to detect the correlation between the miR-302b expression in the pathological specimens and the clinicopathological features by qPCR; the target correlation between miR-302b and DKK1 by immunohistochemistry, qPCR and Western blot; and the correlation between miR-302b and the Wnt/β-catenin signaling pathway by Western blot. The effect of miR-302b on osteoblastogenesis was also studied in a subperiosteal tumorigenesis model of NOD/SCID nude mice.Results: Increased miR-302b suppressed cell proliferation and induced cell apoptosis in RPMI 8226 and MM1.S cells. Targetscan online bioinformatic analysis predicted that miR-302b could bind to 3’UTR of DKK1 mRNA. Target binding of miR-302b to DKK1 was demonstrated by dual-luciferase reporter assay, qPCR, Western blot and immunohistochemistry, indicating that miR-302b was able to degrade DKK1 in RPMI 8226 and MM1.S cells. The model of co-culturing MM cells with preosteoblast MC3T3-E1 cells showed that miR-302b inhibited MM-induced suppression of osteoblast differentiation. Western blotting showed that miR-302b inhibited the Wnt/β-catenin signaling pathway in MM cells. Micro-CT and immunohistochemistry results showed that miR-302b suppressed myeloma bone destruction in vivo.Conclusion: miR-302b targeted DKK1 and inhibited the Wnt/β-catenin signaling pathway in MM.
Eliminating&nbsp;Plasmodium falciparum&nbsp;malaria: results from tailoring active case detection approaches to remote populations in forested border areas in north-eastern Cambodia
Authors: Stratil Ann-Sophie , Vernaeve Lieven , Lopes Sergio , Bourny Yves , Mannion Kylie , Hamade Prudence , Roca-Feltrer Arantxa , Tibenderana James K. , Sovannaroth Siv , Debackere Mark 
Published: February 2021

Abstract
Background Remaining Plasmodium falciparum cases in Cambodia are concentrated in forested border areas and in remote populations who are hard to reach through passive case detection. A key approach to reach these populations is active case detection by mobile malaria workers (MMWs). However, this is operationally challenging because of changing movement patterns of the target population moving into less accessible areas. From January 2018 to December 2020, a tailored package of active case detection approaches was implemented in forested border areas of three provinces in north-eastern Cambodia to reach remote populations and support the elimination of P. falciparum malaria.Methods Key elements of this project were to tailor approaches to local populations, use responsive monitoring systems, maintain operational flexibility, build strong relationships with local communities, and implement close supervision practices. MMWs were recruited from local communities. Proactive case detection approaches included mobile malaria posts positioned at frequented locations around and within forests, and locally informed outreach activities targeting more remote locations. Reactive case detection was conducted among co-travellers of confirmed cases. Testing for malaria was conducted independent of fever symptoms. Routine monitoring of programmatic data informed tactical adaptations, while supervision exercises ensured service quality. Results Despite operational challenges, service delivery sites were able to maintain consistently high testing rates throughout the implementation period, with each of 45 (standard deviation, SD 1) sites testing a monthly average of 64 (SD 6) people in 2020. In 2020, MMWs detected only 32 P. falciparum cases. Over the project period, the P. falciparum/P. vivax ratio steadily inversed. Including data from neighbouring health centres and village malaria workers, 45% (80,988/180,732) of all people tested and 39% (1,280/3,243) of P. falciparum cases detected in the area can be attributed to project MMWs.Remaining challenges: maintaining intensified elimination efforts, addressing the issue of detecting low parasitaemia cases and shifting focus to P. vivax malaria challenge the last phase of malaria elimination.Conclusions Reaching remote populations through active case detection should remain a key strategy to eliminate P. falciparum malaria. This case study presented a successful approach combining tailored proactive and reactive strategies that could be transferred to similar settings in other areas of the Greater Mekong Subregion.
Hematological Profile of Children With Malaria in Sorong, West Papua, Indonesia
Authors: Jiero Syilvia , Pasaribu Ayodhia Pitaloka 
Published: February 2021

Abstract
Background Malaria remains a major public health problem in Indonesian Papua, with children under five years of age being the most affected group. Haematological changes, such as cytopenia that occur during malaria infection have been suggested as potential predictors and can aid in the diagnosis of malaria. This study aimed to assess the haematological alterations associated with malaria infection in children presenting with signs and symptoms of malaria.Methods A retrospective study was performed by collecting data from the medical records of malaria patients at Sorong Regional General Hospital, Sorong, West Papua, Indonesia, both from outpatient and inpatient clinics, from January 2014 until December 2017. The laboratory profile of children suffering from malaria was evaluated. Results One hundred and eighty-two children aged 1 month to 18 years old were enrolled. The subjects were mostly male (112, 61.5%) with a mean age of 6.45 years (SD = 4.3 years). Children below 5 years of age suffered the most from malaria in this study (77,42.3%). One hundred two subjects (56%) were infected with Plasmodium falciparum. Half of the enrolled subjects (50%) had haemoglobin level (Hb) between 5.1 and 10 gr/dL. A total of 41 children (53.2%) less than 5 years old suffered from P. falciparum infection. In the age group of 5-10 years, there were 34 children (57.6%) who suffered from P. falciparum, and in the age group >10 years, 27 children (58.7%) suffered from P. falciparum infection. Only 4 subjects (5.2%) in the less than 5 years old age group had mixed malaria infection. Among eight predictors of the haematological profile, there were five predictors that were significantly associated with the diagnostic criteria, namely haemoglobin, haematocrit, leukocytes, platelets and monocytes (p <0.05). Generally, clinical symptoms are not significantly associated with a malaria diagnosis, and only one variable showed a significant relationship, pale, with a P value of 0.001. Conclusions Children with malaria had changes in some haematological markers, with anaemia, low platelet count, white blood count, and lymphocyte count being the most important predictors of malaria infection in the study area. These markers could be used to raise suspicion of malaria in children living in hogh endemic areas, such as West Papua.
Episode Three: Julietta Singh
Authors: Shah Rajni , Singh Julietta , 周 Gibbons Fili 
Published: February 2021

This episode draws on two different recordings of conversations between Rajni Shah and Julietta Singh, in which they discover and recognise common ground in their lived and embodied experiences while learning to let go of expectations about how the recording process itself might unfold. The structure of this episode is non-linear, inviting the listener on a disorienting and dreamy listening adventure.
In the accompanying offering to this episode, Julietta shares a reading from her new book, The Breaks.
Full credits and transcript for this episode will be published when the episode is released on 13 March 2021.
Urban water demand for manufacturing, construction and service industries: a microdata analysis
Authors: Gracia-de-Rentería Pilar , Barberán Ramón , Mur Jesús 
Published: February 2021

Abstract
This study analyses the industrial demand for urban water using a panel dataset of firms operating in the city of Zaragoza (Spain) and looking at three sectors (manufacturing, construction and services) disaggregated on 24 subsectors. Evidence in favour of using the marginal price rather than the average price is obtained, and the selection of the price is found to influence the value of the elasticities. Based on a translog cost function, the direct price elasticity of water (−0.86), the output elasticity (0.73) and the cross-price elasticities between water and capital, labour and supplies (being all of them substitutes) were estimated. By subsectors, the influence of price is only significant in those with a higher share of water in the total production cost. These results indicate that pricing can be used as a tool for managing water demand by promoting conservation of the resource. However, these results also indicate that the simultaneous use of other instruments is advisable to reinforce the impact of pricing policy on water consumption.
Research on comprehensive evaluation model of rural domestic sewage treatment technology based on fuzzy comprehensive evaluation and analytic hierarchy process method
Authors: Qi-yu Zhang , Zeng-jin Liu , Lai-sheng Liu , Na Li 
Published: February 2021

Abstract
In China, rural domestic sewage treatment has become an urgent problem to be solved to improve the rural human settlement environment. However, there is no scientific, objective, and systematic evaluation model for selecting rural domestic sewage treatment technology. Therefore, this paper mainly studies on the establishment of the evaluation system model for China's typical rural domestic sewage treatment technology and the application of technology selection. Based on the analytic hierarchy process and the life cycle method, the experts consulted and analyzed the factors affecting the evaluation of China's rural sewage treatment technology. The comprehensive evaluation index system suitable for China's rural sewage treatment technology was established based on the analysis results. Combined with the fuzzy comprehensive evaluation method, five typical rural domestic sewage treatment technologies were applied and analyzed. The results show that the comprehensive evaluation of the biofilm technology is best at 3.5669, followed by the septic tank treatment technology and land treatment technology, which are 2.8829 and 2.8422, respectively. The case analysis verifies the applicability of the model, which can support the selection of technologies for the rural domestic sewage treatment market in China.
Influence of the soil water retention curve type and magnetic water treatment on lettuce irrigation management responses
Authors: Tavares Ordones Lemos Lis , Ponciano de Deus Fábio , Silveira Thebaldi Michael , Valentim Diotto Adriano , Carvalho de Andrade Júnior Valter , de Almeida Rodrigo César 
Published: February 2021

Abstract
This study aimed to evaluate the influence of magnetized water use on lettuce irrigation management responses, and based on the generated data, to evaluate by simulation the influence of soil water retention curve type on the lettuce irrigation management responses. This work was divided into three stages: 1 – determination of field and laboratory soil water retention curves; 2 – lettuce crop irrigation management experiment using soil water retention curve with field data, evaluating different soil water tensions to start irrigation and different water types (magnetically treated water, and non-treated water); and 3 – estimation of the irrigation management responses (simulation) using the soil water retention curve performed in the laboratory (using non-treated water), compared with the experimental results (stage 2). The use of magnetically treated water determined the soil moisture maintenance for a longer time and fewer irrigation events, leading to less water being applied and electricity consumption. The use of the soil water retention curve derived from the field data determined less water and electric energy consumption in Lucy Brown lettuce irrigation, in comparison with the simulated use of the soil water retention curve from laboratory data.
A polymer – zeolite composite for mixed metal removal from aqueous solution
Authors: Yıldız Yiğit Merve , Baran Esra Sultan , Moral Çiğdem Kıvılcımdan 
Published: February 2021

Abstract
Heavy metals become inevitable pollutants that are toxic to life. Lots of treatment methods are available; adsorption is a cheap option. Metals are mostly found as mixtures in wastewaters. Taking this into account, a natural composite adsorbent aims to remove multiple heavy metals (Pb2+, Cu2+, Cd2+). Alginate was combined with clinoptilolite to form alginate – clinoptilolite (A–C) beads. First, factors influencing the removal efficiency of metals were investigated. Then, continuous column experiments were performed to evaluate the real application potential of the adsorbent. A–C beads preferably adsorbed Pb2+. Batch experiments showed metal uptake reached equilibrium after 24 hours and kinetics were compatible with the first-order. Also, pH values near neutral levels were observed to increase heavy metal removal. On the other hand, adsorption equilibrium was well described by the Langmuir model for Cu2+ and Cd2+ and by the Freundlich model for Pb2+. The highest heavy metal uptake was calculated as 2,145 mg /g A–C beads for Pb2+. Continuous column operations were suggested to apply low flow rates (&lt;2 mL/min) and heavy metal concentration (&lt;10 mg/L) for effectiveness. A–C beads can be a good candidate for mixed heavy metal removal composed of environmentally friendly and low-cost materials.