bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do Chinese people perceive their healthcare system? Trends and determinants of public satisfaction and perceived fairness, 2006–2019
Authors: Zhu Yishan , Li Yuanyuan , Wu Ming , Fu Hongqiao 
Published: January 2022

Abstract
Background
The public’s perception of the health system provides valuable insights on health system performance and future directions of improvement. While China’s health care reform was a response to people’s discontent in the health care system due to the lack of accessibility and affordability, little is known on changes in public perception of China’s health system. This paper examines trends in public perception of the health system between 2006 and 2019 and assesses determinants of public perception in China’s health system.

Methods
Seven waves of the China Social Survey, a nationally representative survey, were used to examine trends in public satisfaction with health care and perceived fairness in health care. Chi-square tests were used to examine differences across waves. Logistic regression models were used to explore determinants of public perception, including variables on sociodemographic characteristics, health system characteristics, and patient experience.

Results
Satisfaction with health care increased from 57.76% to 77.26% between 2006 and 2019. Perceived fairness in health care increased from 49.79% to 72.03% during the same period. Both indicators showed that the major improvement occurred before 2013. Sociodemographic characteristics are weakly associated with public perception. Financial protection and perceived medical safety are strongly associated with public perception, while accessibility is weakly associated with public perception. Patient experience such as perceived affordability and quality in the last medical visit are strongly associated with public perception of the health care system, while the accessibility of the last medical visit shows no impacts.

Conclusion
Public satisfaction on health care and perceived fairness in health care in China improved over 2006–2019. The main improvement occurred in accordance with huge financial investments in public health insurance before 2013. Financial protection and perceived quality play significant roles in determining public perception, whereas accessibility and sociodemographic characteristics have limited influence on people’s perception of China’s health system. To achieve higher satisfaction and a higher sense of fairness in health care, China’s health system needs to continue its reforms on hospital incentives and integrated delivery system to control health expenditure and improve health care quality.
Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection
Authors: Hwang Yu-Chyi , Lu Ruei-Min , Su Shih-Chieh , Chiang Pao-Yin , Ko Shih-Han , Ke Feng-Yi , Liang Kang-Hao , Hsieh Tzung-Yang , Wu Han-Chung 
Published: January 2022

AbstractThe coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity and reliability, monoclonal antibodies (mAbs) have emerged as powerful tools to treat and detect numerous diseases. Hence, many researchers have begun to urgently develop Ab-based kits for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ab drugs for use as COVID-19 therapeutic agents. The detailed structure of the SARS-CoV-2 spike protein is known, and since this protein is key for viral infection, its receptor-binding domain (RBD) has become a major target for therapeutic Ab development. Because SARS-CoV-2 is an RNA virus with a high mutation rate, especially under the selective pressure of aggressively deployed prophylactic vaccines and neutralizing Abs, the use of Ab cocktails is expected to be an important strategy for effective COVID-19 treatment. Moreover, SARS-CoV-2 infection may stimulate an overactive immune response, resulting in a cytokine storm that drives severe disease progression. Abs to combat cytokine storms have also been under intense development as treatments for COVID-19. In addition to their use as drugs, Abs are currently being utilized in SARS-CoV-2 detection tests, including antigen and immunoglobulin tests. Such Ab-based detection tests are crucial surveillance tools that can be used to prevent the spread of COVID-19. Herein, we highlight some key points regarding mAb-based detection tests and treatments for the COVID-19 pandemic.
Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved β-carotene production in Saccharomyces cerevisiae
Authors: Bu Xiao , Lin Jing‑Yuan , Duan Chang‑Qing , Koffas Mattheos A. G. , Yan Guo‑Liang 
Published: January 2022

Abstract
Background
The limitation of storage space, product cytotoxicity and the competition for precursor are the major challenges for efficiently overproducing carotenoid in engineered non-carotenogenic microorganisms. In this work, to improve β-carotene accumulation in Saccharomyces cerevisiae, a strategy that simultaneous increases cell storage capability and strengthens metabolic flux to carotenoid pathway was developed using exogenous oleic acid (OA) combined with metabolic engineering approaches.

Results
The direct separation of lipid droplets (LDs), quantitative analysis and genes disruption trial indicated that LDs are major storage locations of β-carotene in S. cerevisiae. However, due to the competition for precursor between β-carotene and LDs-triacylglycerol biosynthesis, enlarging storage space by engineering LDs related genes has minor promotion on β-carotene accumulation. Adding 2 mM OA significantly improved LDs-triacylglycerol metabolism and resulted in 36.4% increase in β-carotene content. The transcriptome analysis was adopted to mine OA-repressible promoters and IZH1 promoter was used to replace native ERG9 promoter to dynamically down-regulate ERG9 expression, which diverted the metabolic flux to β-carotene pathway and achieved additional 31.7% increase in β-carotene content without adversely affecting cell growth. By inducing an extra constitutive β-carotene synthesis pathway for further conversion precursor farnesol to β-carotene, the final strain produced 11.4 mg/g DCW and 142 mg/L of β-carotene, which is 107.3% and 49.5% increase respectively over the parent strain.

Conclusions
This strategy can be applied in the overproduction of other heterogeneous FPP-derived hydrophobic compounds with similar synthesis and storage mechanisms in S. cerevisiae.

Graphical Abstract
The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer
Authors: Chen Lingyan , Dong Jianfeng , Li Zeying , Chen Yu , Zhang Yan 
Published: January 2022

Abstract
Background
It has been revealed that B7H4 is negatively correlated with PDL1 and identifies immuno-cold tumors in glioma. However, the application of the B7H4-PDL1 classifier in cancers has not been well testified.

Methods
A pan-cancer analysis was conducted to evaluate the immunological role of B7H4 using the RNA-sequencing data downloaded from the Cancer Genome Atlas (TCGA). Immunohistochemistry (IHC) and multiplexed quantitative immunofluorescence (QIF) were performed to validate the primary results revealed by bioinformatics analysis.

Results
The pan-cancer analysis revealed that B7H4 was negatively correlated with PDL1 expression and immune cell infiltration in CeCa. In addition, patients with high B7H4 exhibited the shortest overall survival (OS) and relapse-free survival (RFS) while those with high PDL1 exhibited a better prognosis. Multiplexed QIF showed that B7H4 was mutually exclusive with PDL1 expression and the B7H4-high group exhibited the lowest CD8 + T cell infiltration. Besides, B7H4-high predicted highly proliferative subtypes, which expressed the highest Ki67 antigen. Moreover, B7H4-high also indicated a lower response to multiple therapies.

Conclusions
Totally, the B7H4-PDL1 classifier identifies the immunogenicity and predicts proliferative subtypes and limited therapeutic options in CeCa, which may be a convenient and feasible biomarker in clinical practice.
Plasmodium falciparum histidine rich protein 2 (pfhrp2): an additional genetic marker suitable for anti-malarial drug efficacy trials
Authors: Atroosh Wahib M. , Lau Yee-Ling , Snounou Georges , Azzani Meram , Al-Mekhlafi Hesham M. 
Published: January 2022

Abstract
Background
Genotyping of the three Plasmodium falciparum polymorphic genes, msp1, msp2 and glurp, has been adopted as a standard strategy to distinguish recrudescence from new infection in drug efficacy clinical trials. However, the suitability of a particular gene is compromised in areas where its allelic variants distribution is significantly skewed, a phenomenon that might occur in isolated parasite populations or in areas of very low transmission. Moreover, observation of amplification bias has diminished the value of glurp as a marker.

Methods
The suitability of the polymorphic P. falciparum histidine-rich protein 2 (pfhrp2) gene was assessed to serve as an alternative marker using a PCR-sequencing or a PCR–RFLP protocol for genotyping of samples in drug efficacy clinical trials. The value of pfhrp2 was validated by side-by-side analyses of 5 admission-recrudescence sample pairs from Yemeni malaria patients.

Results
The outcome of the single pfhrp2 gene discrimination analysis has been found consistent with msp1, msp2 and glurp pool genotyping analysis for the differentiation of recrudescence from new infection.

Conclusion
The findings suggest that under the appropriate circumstances, pfhrp2 can serve as an additional molecular marker for monitoring anti-malarials efficacy. However, its use is restricted to endemic areas where only a minority of P. falciparum parasites lack the pfhrp2 gene.
Safety of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials
Authors: Assefa Dawit Getachew , Zeleke Eden Dagnachew , Molla Wondwosen , Mengistu Nebiyu , Sefa Ahmedin , Mebratu Andualem , Bate Asresu Feleke , Bekele Etaferaw , Yesmaw Gizachew , Makonnen Eyasu 
Published: January 2022

Abstract
Background
The efficacies of artemisinin based combinations have been excellent in Africa, but also comprehensive evidence regarding their safety would be important. The aim of this review was to synthesize available evidence on the safety of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa.

Methods
A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL) for retrieving randomized control trials comparing safety of DHA-PQ and AL for treatment of uncomplicated P. falciparum malaria among children in Africa. The search was performed from August 2020 to 30 April 2021. Using Rev-Man software (V5.4.1), the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI).

Results
In this review, 18 studies were included, which involved 10,498 participants were included. Compared to AL, DHA-PQ was associated with a slightly higher frequency of early vomiting (RR 2.26, 95% CI 1.46 to 3.50; participants = 7796; studies = 10; I2 = 0%, high quality of evidence), cough (RR 1.06, 95% CI 1.01 to 1.11; participants = 8013; studies = 13; I2 = 0%, high quality of evidence), and diarrhoea (RR 1.16, 95% CI 1.03 to 1.31; participants = 6841; studies = 11; I2 = 8%, high quality of evidence) were more frequent in DHA-PQ treatment arm.

Conclusion
From this review, it can be concluded that early vomiting, diarrhoea, and cough were common were significantly more frequent in patients who were treated with the DHA-PQ than that of AL, and both drugs are well tolerated. More studies comparing AL with DHA-PQ are needed to determine the comparative safety of these drugs.
Switching to nanonutrients for sustaining agroecosystems and environment: the challenges and benefits in moving up from ionic to particle feeding
Authors: Bhardwaj Ajay Kumar , Arya Geeta , Kumar Raj , Hamed Lamy , Pirasteh-Anosheh Hadi , Jasrotia Poonam , Kashyap Prem Lal , Singh Gyanendra Pratap 
Published: January 2022

AbstractThe worldwide agricultural enterprise is facing immense pressure to intensify to feed the world’s increasing population while the resources are dwindling. Fertilizers which are deemed as indispensable inputs for food, fodder, and fuel production now also represent the dark side of the intensive food production system. With most crop production systems focused on increasing the quantity of produce, indiscriminate use of fertilizers has created havoc for the environment and damaged the fiber of the biogeosphere. Deteriorated nutritional quality of food and contribution to impaired ecosystem services are the major limiting factors in the further growth of the fertilizer sector. Nanotechnology in agriculture has come up as a better and seemingly sustainable solution to meet production targets as well as maintaining the environmental quality by use of less quantity of raw materials and active ingredients, increased nutrient use-efficiency by plants, and decreased environmental losses of nutrients. However, the use of nanofertilizers has so far been limited largely to controlled environments of laboratories, greenhouses, and institutional research experiments; production and availability on large scale are still lagging yet catching up fast. Despite perceivable advantages, the use of nanofertilizers is many times debated for adoption at a large scale. The scenario is gradually changing, worldwide, towards the use of nanofertilizers, especially macronutrients like nitrogen (e.g. market release of nano-urea to replace conventional urea in South Asia), to arrest environmental degradation and uphold vital ecosystem services which are in critical condition. This review offers a discussion on the purpose with which the nanofertilizers took shape, the benefits which can be achieved, and the challenges which nanofertilizers face for further development and real-world use, substantiated with the significant pieces of scientific evidence available so far.Graphical Abstract
Drug delivery of 6-bromoindirubin-3’-glycerol-oxime ether employing poly(d,l-lactide-co-glycolide)-based nanoencapsulation techniques with sustainable solvents
Authors: Czapka Anna , Grune Christian , Schädel Patrick , Bachmann Vivien , Scheuer Karl , Dirauf Michael , Weber Christine , Skaltsounis Alexios-Leandros , Jandt Klaus D. , Schubert Ulrich S. , Fischer Dagmar , Werz Oliver 
Published: January 2022

Abstract
Background
Insufficient solubility and stability of bioactive small molecules as well as poor biocompatibility may cause low bioavailability and are common obstacles in drug development. One example of such problematic molecules is 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE), a hydrophobic indirubin derivative. 6BIGOE potently modulates the release of inflammatory cytokines and lipid mediators from isolated human monocytes through inhibition of glycogen synthase kinase-3 in a favorable fashion. However, 6BIGOE suffers from poor solubility and short half-lives in biological aqueous environment and exerts cytotoxic effects in various mammalian cells. In order to overcome the poor water solubility, instability and cytotoxicity of 6BIGOE, we applied encapsulation into poly(d,l-lactide-co-glycolide) (PLGA)-based nanoparticles by employing formulation methods using the sustainable solvents Cyrene™ or 400 g/mol poly(ethylene glycol) as suitable technology for efficient drug delivery of 6BIGOE.

Results
For all preparation techniques the physicochemical characterization of 6BIGOE-loaded nanoparticles revealed comparable crystallinity, sizes of about 230 nm with low polydispersity, negative zeta potentials around − 15 to − 25 mV, and biphasic release profiles over up to 24 h. Nanoparticles with improved cellular uptake and the ability to mask cytotoxic effects of 6BIGOE were obtained as shown in human monocytes over 48 h as well as in a shell-less hen’s egg model. Intriguingly, encapsulation into these nanoparticles fully retains the anti-inflammatory properties of 6BIGOE, that is, favorable modulation of the release of inflammation-relevant cytokines and lipid mediators from human monocytes.

Conclusions
Our formulation method of PLGA-based nanoparticles by applying sustainable, non-toxic solvents is a feasible nanotechnology that circumvents the poor bioavailability and biocompatibility of the cargo 6BIGOE. This technology yields favorable drug delivery systems for efficient interference with inflammatory processes, with improved pharmacotherapeutic potential.

Graphical Abstract
Sustainable synthesis of microwave-assisted IONPs using Spinacia oleracea L. for control of fungal wilt by modulating the defense system in tomato plants
Authors: Ashraf Hina , Anjum Tehmina , Riaz Saira , Batool Tanzeela , Naseem Shahzad , Li Guihua 
Published: January 2022

AbstractBackgroundChanging climate enhances the survival of pests and pathogens, which eventually affects crop yield and reduces its economic value. Novel approaches should be employed to ensure sustainable food security. Nano-based agri-chemicals provide a distinctive mechanism to increase productivity and manage phytopathogens, with minimal environmental distress. In vitro and in greenhouse studies were conducted to evaluate the potential of green-synthesized iron-oxide nanoparticles (IONPs) in suppressing wilt infection caused byFusarium oxysporumf. sp.lycospersici, and improving tomato growth (Solanum lycopersicum) and fruit quality.ResultsVarious microwave powers (100–1000 W) were used to modulate the properties of the green-synthesized IONPs, using spinach as a starting material. The IONPs stabilized with black coffee extract were substantively characterized using X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy, dielectric and impedance spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning and transmission electron microscopy (SEM and TEM, respectively), and magnetization analysis. XRD revealed a cubic magnetite (Fe3O4) phase with super-paramagnetic nature, detected at all microwave powers. The binding energies of Fe 2p3/2(710.9 eV) and Fe 2p1/2(724.5 eV) of Fe3O4NPs were confirmed using XPS analysis at a microwave power of 1000 W. Uniform, spherical/cubical-shaped particles with an average diameter of 4 nm were confirmed using SEM and TEM analysis. A significant reduction in mycelial growth and spore germination was observed upon exposure to different IONP treatments. Malformed mycelium, DNA fragmentation, alternation in the cell membrane, and ROS production inF. oxysporumindicated the anti-microbial potential of the IONPs. The particles were applied both through the root (before transplantation) and by means of foliar application (after two weeks) to the infected seedlings. IONPs significantly reduced disease severity by an average of 47.8%, resulting in increased plant growth variables after exposure to 12.5 µg/mL of IONPs. Analysis of photosynthetic pigments, phenolic compounds, and anti-oxidant enzymes in the roots and shoots showed an increasing trend after exposure to various concentrations of IONPs. Correspondingly, lycopene, vitamin C, total flavonoids, and protein content were substantially improved in tomato fruits after treatment with IONPs.ConclusionThe findings of the current investigation suggested that the synthesized IONPs display anti-fungal and nutritional properties that can help to manage Fusarium wilt disease, resulting in enhanced plant growth and fruit quality.Graphical Abstract
Nano delivery of simvastatin targets liver sinusoidal endothelial cells to remodel tumor microenvironment for hepatocellular carcinoma
Authors: Yu Zhuo , Guo Jianfeng , Liu Yun , Wang Menglin , Liu Zhengsheng , Gao Yueqiu , Huang Leaf 
Published: January 2022

Abstract
Background
Hepatocellular carcinoma (HCC) developed in fibrotic liver does not respond well to immunotherapy, mainly due to the stromal microenvironment and the fibrosis-related immunosuppressive factors. The characteristic of liver sinusoidal endothelial cells (LSECs) in contributing to fibrosis and orchestrating immune response is responsible for the refractory to targeted therapy or immunotherapy of HCC. We aim to seek a new strategy for HCC treatment based on an old drug simvastatin which shows protecting effect on LSEC.

Method
The features of LSECs in mouse fibrotic HCC model and human HCC patients were identified by immunofluorescence and scanning electron microscopy. The effect of simvastatin on LSECs and hepatic stellate cells (HSCs) was examined by immunoblotting, quantitative RT-PCR and RNA-seq. LSEC-targeted delivery of simvastatin was designed using nanotechnology. The anti-HCC effect and toxicity of the nano-drug was evaluated in both intra-hepatic and hemi-splenic inoculated mouse fibrotic HCC model.

Results
LSEC capillarization is associated with fibrotic HCC progression and poor survival in both murine HCC model and HCC patients. We further found simvastatin restores the quiescence of activated hepatic stellate cells (aHSCs) via stimulation of KLF2-NO signaling in LSECs, and up-regulates the expression of CXCL16 in LSECs. In intrahepatic inoculated fibrotic HCC mouse model, LSEC-targeted nano-delivery of simvastatin not only alleviates LSEC capillarization to regress the stromal microenvironment, but also recruits natural killer T (NKT) cells through CXCL16 to suppress tumor progression. Together with anti-programmed death-1-ligand-1 (anti-PD-L1) antibody, targeted-delivery of simvastatin achieves an improved therapeutic effect in hemi-splenic inoculated advanced-stage HCC model.

Conclusions
These findings reveal an immune-based therapeutic mechanism of simvastatin for remodeling immunosuppressive tumor microenvironment, therefore providing a novel strategy in treating HCC.

Graphical Abstract
Turing miRNA into infinite coordination supermolecule: a general and enabling nanoengineering strategy for resurrecting nuclear acid therapeutics
Authors: Li Liya , He Wangxiao , You Weiming , Yan Jin , Liu Wenjia 
Published: January 2022

Abstract
Background
Clinical translation of therapeutic nuclear acid, particularly those targeting tumor progression, has been hampered by the intrinsic weaknesses of nuclear acid therapeutic including poor systemic stability, rapid clearance, low membrane permeability and lack of targeting ability. Small nuclear acid engineered into carrier-free nanodrugs with structural stability and disease targeting may be viable to overcome pharmaceutical obstacles of nuclear acid.

Methods
A general method through a mild and simple chemistry was established to convert therapeutic miRNA into an infinite Auric-sulfhydryl coordination supramolecular miRNA termed IacsRNA with near-spherical nanostructure, high colloid as well as anti-hydrolysis stability and low macrophage uptakes.

Results
IacsRNA presented the increased half-life period in circulation and accumulation at tumor sites in comparison to normal miRNA. Moreover, Iacs-miR-30c showed no toxicity of viscera and sanguis system in the 5-time injection dosage of the treatment. More importantly, Iacs-miR-30c potently suppressed the Wnt signaling pathway in vitro and in vivo, and effectively sensitized both potency of 5-Fu in PDX model of colon cancer and Anti-PD1 in B16F10 homograft model of melanoma.

Conclusion
Collectively, this work amply confirmed the design of IacsRNA as a general and viable strategy of nano-pharmaceutic to concert flimsy therapeutic miRNA into potential drugs. Considering from a broader perspective, the miRNA-initiated infinite coordination self-assembly strategy has distinct advantages in resurrecting nuclear acid therapeutics, probably bringing new inspiration to RNA-derived therapeutics of a great variety of human diseases including cancer.

Graphical Abstract