bluuebunny/crossref_metadata_2025 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

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

The 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

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

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

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

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

The 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

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

Background

Changing 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.

Results

Various 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.

Conclusion

The 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

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

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
Hyperandrogenism and menstrual imbalance are the best predictors of metformin response in PCOS patients
Authors: Garzia Emanuele , Galiano Valentina , Marfia Giovanni , Navone Stefania , Grossi Enzo , Marconi Anna Maria
Published: January 2022

Background

Moving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels. Inconsistency and unpredictability of response to metformin limit its extensive use. Aim of this study was to identify reliable predictors of response to metformin therapy for weight loss and reduction in plasma androgen levels using ANNs (artificial neural networks).

Methods

One hundred eight consecutive women with PCOS (ESHRE/ASRM 2003 Rotterdam criteria) treated with metformin 1500 mg/day, at inclusion and every 6 months underwent to a complete clinical, endocrine/metabolic assessment and ultrasonographic evaluation. Therapy outcomes were BMI reduction (≥1 kg/m2) in overweight/obese and free-androgen-index (FAI) decrease (≥1%) in hyperandrogenemic women. Semantic connectivity maps (SCMs) were obtained through Auto-CM, a fourth generation ANN, to compare patients’ baseline clinical features to the treatment outcomes. Multivariate logistic regression analysis was used to assess the major predictor in drop-out patients and the associated risk.

Results

At 6 months 54 out of 103 (52,4%) obese patients showed BMI reduction and 45 out of 89 (50,6%) hyperandrogenemic women showed FAI decrease. The further response rates at 12 months were 30,6 and 47%, respectively. SCMs showed a clear polarization for both the outcomes with elevated accuracy. Treatment responsiveness resulted strictly related to oligo-amenorrhea and hyperandrogenemia at baseline. In addition, lower serum testosterone levels at baseline were found to be the major predictor of treatment discontinuation.

Conclusions

In women with PCOS, menstrual pattern imbalance and ovarian androgens excess are the best predictors of metformin response. They may pave the way for a rethinking of the criteria for evaluating hyperandrogenism in order to better define the large population included in the diagnosis of PCOS. Baseline plasma testosterone level can serve as a sensitive marker to predict treatment compliance.
Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
Authors: Al Omran Alzahra J. , Shao Amy S. , Watanabe Saki , Zhang Zeyu , Zhang Jifeng , Xue Chen , Watanabe Junji , Davies Daryl L. , Shao Xuesi M. , Liang Jing
Published: January 2022

Background

Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system.

Methods

Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured.

Results

Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes.

Conclusion

The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.
Health risks and mitigation strategies from occupational exposure to wildland fire: a scoping review
Authors: Koopmans Erica , Cornish Katie , Fyfe Trina M. , Bailey Katherine , Pelletier Chelsea A.
Published: January 2022

Objectives

Due to accelerating wildland fire activity, there is mounting urgency to understand, prevent, and mitigate the occupational health impacts associated with wildland fire suppression. The objectives of this review of academic and grey literature were to:

Identify the impact of occupational exposure to wildland fires on physical, mental, and emotional health; and

Examine the characteristics and effectiveness of prevention, mitigation, or management strategies studied to reduce negative health outcomes associated with occupational exposure to wildland fire.

Methods

Following established scoping review methods, academic literature as well as government and industry reports were identified by searching seven academic databases and through a targeted grey literature search. 4679 articles were screened using pre-determined eligibility criteria. Data on study characteristics, health outcomes assessed, prevention or mitigation strategies studied, and main findings were extracted from each included document. The results of this scoping review are presented using descriptive tables and a narrative summary to organize key findings.

Results

The final sample was comprised of 100 articles: 76 research articles and 24 grey literature reports. Grey literature focused on acute injuries and fatalities. Health outcomes reported in academic studies focused on respiratory health (n = 14), mental health (n = 16), and inflammation and oxidative stress (n = 12). The identified studies evaluated short-term outcomes measuring changes across a single shift or wildland fire season. Most research was conducted with wildland firefighters and excluded personnel such as aviation crews, contract crews, and incident management teams. Five articles reported direct study of mitigation strategies, focusing on the potential usage of masks, advanced hygiene protocols to reduce exposure, fluid intake to manage hydration and core temperature, and glutamine supplementation to reduce fatigue.

Conclusions

While broad in scope, the evidence base linking wildland fire exposure to any one health outcome is limited. The lack of long-term evidence on changes in health status or morbidity is a clear evidence gap and there is a need to prioritize research on the mental and physical health impact of occupational exposure to wildland fire.
High throughput phenotyping of cross-sectional morphology to assess stalk lodging resistance
Authors: Oduntan Yusuf A. , Stubbs Christopher J. , Robertson Daniel J.
Published: January 2022

Background

Stalk lodging (mechanical failure of plant stems during windstorms) leads to global yield losses in cereal crops estimated to range from 5% to 25% annually. The cross-sectional morphology of plant stalks is a key determinant of stalk lodging resistance. However, previously developed techniques for quantifying cross-sectional morphology of plant stalks are relatively low-throughput, expensive and often require specialized equipment and expertise. There is need for a simple and cost-effective technique to quantify plant traits related to stalk lodging resistance in a high-throughput manner.

Results

A new phenotyping methodology was developed and applied to a range of plant samples including, maize (Zea mays), sorghum (Sorghum bicolor), wheat (Triticum aestivum), poison hemlock (Conium maculatum), and Arabidopsis (Arabis thaliana). The major diameter, minor diameter, rind thickness and number of vascular bundles were quantified for each of these plant types. Linear correlation analyses demonstrated strong agreement between the newly developed method and more time-consuming manual techniques (R2 > 0.9). In addition, the new method was used to generate several specimen-specific finite element models of plant stalks. All the models compiled without issue and were successfully imported into finite element software for analysis. All the models demonstrated reasonable and stable solutions when subjected to realistic applied loads.

Conclusions

A rapid, low-cost, and user-friendly phenotyping methodology was developed to quantify two-dimensional plant cross-sections. The methodology offers reduced sample preparation time and cost as compared to previously developed techniques. The new methodology employs a stereoscope and a semi-automated image processing algorithm. The algorithm can be used to produce specimen-specific, dimensionally accurate computational models (including finite element models) of plant stalks.
Market access of Chinese patent medicine products to healthcare security system in China: implications for international integration of traditional medicine into health systems
Authors: Xia Chenglai , Yao Dongning , Lai Yunfeng , Xue Yan , Hu Hao
Published: January 2022

Background

China has introduced a series of polices and practice to manage the market access of Chinese patent medicine (CPM) products into its healthcare security system, which is less analyzed and reported in current literature. Therefore, this paper aimed to investigate the mechanisms managing market access of CPM products into healthcare security system in China, expecting to provide implications for international integration of traditional medicine products into health systems.

Method

This paper used a documentary analysis approach as a qualitative research method. Data were collected from four sources and analyzed in a thematic way.

Results

Four mechanisms to manage entry, price adjustment, and exit of innovative brand and generic CPM products are identified, including: (1) price negotiation, mechanism of new entry of innovative brand CPM products into the national reimbursement list; (2) price re-negotiation, mechanism of price adjustment of innovative brand CPM products within the national reimbursement list; (3) mass procurement, mechanism of generic CPM products to healthcare security system; and (4) direct removal, mechanism of removal from the national reimbursement list.

Conclusions

China has established market access framework of CPM products by focusing on price negotiation for innovative brand CPM products and mass procurement for generic CPM products. Further studies of CPM products based real-world data are needed to provide clinical and pharmacoeconomic evidence to support market access of CPM products into healthcare security systems.
Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation
Authors: Ma Zhaochen , Liu Yudong , Li Congchong , Zhang Yanqiong , Lin Na
Published: January 2022

Background

Growing clinical evidences show the potentials of Colquhounia root tablet (CRT) in alleviating diabetic kidney disease (DKD). However, its pharmacological properties and underlying mechanisms remain unclear.

Methods

‘Drug target-Disease gene’ interaction network was constructed and the candidate network targets were screened through evaluating node genes' topological importance. Then, a DKD rat model induced by high-fat diet/streptozotocin was established and used to determine pharmacological effects and network regulatory mechanisms of CRT against DKD, which were also verified using HK2 cell model induced by high glucose.

Results

The candidate network targets of CRT against DKD were involved into various type II diabetes-related and nephropathy-related pathways. Due to the topological importance of the candidate network targets and the important role of the imbalance between immunity and inflammation in the pathogenesis of DKD, PI3K/AKT/NF-кB signaling-mediated immune-modulatory and anti-inflammatory actions of CRT were selected to be experimentally verified. On the basis of high-fat diet (HFD) / streptozotocin (STZ)-induced DKD rat model, CRT effectively reduced the elevated level of blood glucose, decreased the accumulation of renal lipid, suppressed inflammation and the generation of ECM proteins, and ameliorated kidney function and the renal histopathology through inhibiting the activation of PI3K, AKT and NF-кB proteins, reducing the nuclear accumulation of NF-кB protein and the serum levels of downstream cytokines, which were in line with the in vitro findings.

Conclusions

Our data suggest that CRT may be the promising candidate drug for treating DKD via reversing the imbalance of immune-inflammation system mediated by the PI3K/AKT/NF-кB/IL-1β/TNF-α signaling.
Qingwei San treats oral ulcer subjected to stomach heat syndrome in db/db mice by targeting TLR4/MyD88/NF-κB pathway
Authors: Shi Lu , An Yongcheng , Cheng Long , Li Yiyang , Li Huimin , Wang Chen , Lv Yinglan , Duan Yuhui , Dai Hongyu , He Changhao , Zhang Huilin , Huang Yan , Fu Wanxin , Wang ShengPeng , Zhao Baosheng , Wang Yitao , Zhao Yonghua
Published: January 2022

Background

Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigated the pharmacological mechanisms.

Methods

The main components of QWS aqueous extract were analyzed by LC–MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin–eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B2 (TXB2), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting.

Results

A total of 183 compounds in QWS were identified by LC–MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB2 and the ratio of TXB2/6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4, TRAF6, MyD88, p-IκΒα and NF-κB p65 were decreased.

Conclusion

QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.
The attitude of patients with progressive ataxias towards clinical trials
Authors: Thomas-Black Gilbert , Dumitrascu Andrada , Garcia-Moreno Hector , Vallortigara Julie , Greenfield Julie , Hunt Barry , Walther Susan , Wells Mackenzie , Lynch David R. , Montgomery Hugh , Giunti Paola
Published: January 2022

Background

The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences.

Methods

We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status.

Results

Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration.

Conclusions

Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.
A post pandemic roadmap toward remote assessment for neuromuscular disorders: limitations and opportunities
Authors: Montes Jacqueline , Eichinger Katy J. , Pasternak Amy , Yochai Cara , Krosschell Kristin J.
Published: January 2022

Recent advances in technology and expanding therapeutic opportunities in neuromuscular disorders has resulted in greater interest in and development of remote assessments. Over the past year, the rapid and abrupt COVID-19 shutdowns and stay-at-home orders imposed challenges to routine clinical management and clinical trials. As in-person services were severely limited, clinicians turned to remote assessments through telehealth to allow for continued care. Typically, disease-specific clinical outcome assessments (COAs) for neuromuscular disorders (NMD) are developed over many years through rigorous and iterative processes to fully understand their psychometric properties. While efforts were underway towards developing remote assessments for NMD before the pandemic, few if any were fully developed or validated. These included assessments of strength, respiratory function and patient-reported outcomes, as well as wearable technology and other devices to quantify physical activity and function. Without many choices, clinicians modified COAs for a virtual environment recognizing it was not yet known how they compared to standard in-person administration. Despite being able to quickly adapt to the demands of the COVID-19 pandemic, these experiences with remote assessments uncovered limitations and opportunities. It became clear that existing COAs required modifications for use in a virtual environment limiting the interpretation of the information gathered. Still, the opportunity for real-world evaluation and reduced patient burden were clear benefits to remote assessment and may provide a more robust understanding and characterization of disease impact in NMD. Hence, we propose a roadmap navigating an informed post-pandemic path toward development and implementation of safe and successful use of remote assessments for patients with NMD.
The emergence of molecular systems neuroscience
Authors: Shen Yang , Luchetti Alessandro , Fernandes Giselle , Do Heo Won , Silva Alcino J.
Published: January 2022

Systems neuroscience is focused on how ensemble properties in the brain, such as the activity of neuronal circuits, gives rise to internal brain states and behavior. Many of the studies in this field have traditionally involved electrophysiological recordings and computational approaches that attempt to decode how the brain transforms inputs into functional outputs. More recently, systems neuroscience has received an infusion of approaches and techniques that allow the manipulation (e.g., optogenetics, chemogenetics) and imaging (e.g., two-photon imaging, head mounted fluorescent microscopes) of neurons, neurocircuits, their inputs and outputs. Here, we will review novel approaches that allow the manipulation and imaging of specific molecular mechanisms in specific cells (not just neurons), cell ensembles and brain regions. These molecular approaches, with the specificity and temporal resolution appropriate for systems studies, promise to infuse the field with novel ideas, emphases and directions, and are motivating the emergence of a molecularly oriented systems neuroscience, a new discipline that studies how the spatial and temporal patterns of molecular systems modulate circuits and brain networks, and consequently shape the properties of brain states and behavior.
Early, biomarker-guided steroid dosing in COVID-19 Pneumonia: a pilot randomized controlled trial
Authors: Odeyemi Yewande E. , Chalmers Sarah J. , Barreto Erin F. , Jentzer Jacob C. , Gajic Ognjen , Yadav Hemang
Published: January 2022

ClinicalTrials.gov identifier (NCT number): NCT03852537, Registered February 25, 2019.
Acupuncture for prostatectomy incontinence: study protocol for a multicenter single-blind randomized parallel controlled trial
Authors: Zhang Yao , Guo Shanqi , Wang Chaoran , Liu Xiaodi , Liu Yan , Shang Hongcai , Yang Peiying , Wang Liang , Zhai Jingbo , Li Xiaojiang , Jia Yingjie
Published: January 2022

Background

Urinary incontinence is a common complication post radical prostatectomy. Acupuncture is considered an effective treatment for post-prostatectomy incontinence (PPI), but the evidence is still limited. We propose to evaluate the effectiveness of acupuncture in a rigorously conducted trial.

Methods

Twenty hospitals will recruit 340 participants with urinary incontinence after radical prostatectomy in China from April 2021 to April 2022. Participants will be randomly allocated to acupuncture or sham acupuncture with a 1:1 ratio using computerized simple random sampling. The study plan consists of 1-week baseline, 6-week treatment, and 18-week follow-up. Eighteen 30-min sessions of acupuncture or sham acupuncture treatment will be provided between weeks 1 and 6. The primary outcome is the change in the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF) score at the week 6 from the baseline. Secondary outcomes include the change in volume of urine leakage at weeks 4 and 6 from a baseline measured using the 1-h pad test; 72-h incontinence episode frequency based on a 72-h voiding diary; change in the Expanded prostate cancer Index Composite scale (EPIC-26); change in the Self-Rating Anxiety Scale; weekly consumption of pads; and the severity of urinary incontinence based on a 72-h bladder diary and self-assessment of the therapeutic effect. The safety of acupuncture will also be assessed.

Discussion

This trial will help to identify whether acupuncture is effective for PPI, and, if so, whether it exerts a therapeutic rather than a placebo effect.

Trial Registration

www.Chictr.org.cnChiCTR2100042500. Retrospectively registered on 22 January 2021.