bluuebunny/crossref_metadata_2025 huggingface dataset:
How government health insurance coverage of novel anti-cancer medicines benefited patients in China – a retrospective analysis of hospital clinical data
Authors: Diao Yifan , Lin Mengbo , Xu Kai , Huang Ji , Wu Xiongwei , Li Mingshuang , Sun Jing , Li Hong
Published: August 2021

Background

China started to cover novel medicines for the treatment of major cancers, such as trastuzumab for breast cancer by the government health insurance programs since 2016. Limited data have been published on the use of cancer medications and little is known about how government health insurance coverage of novel anti-cancer medicines benefited patients in the real world. This study aimed to generate evidence to inform the health security authorities to optimize the government health insurance coverage of novel anti-cancer medicines as a more inclusive and equal policy, through which each of the needed patient can get access to the novel anti-cancer medicines regardless of the ability to pay.

Methods

The study targeted one of the government health insurance newly covered novel medicines for breast cancer and the breast cancer patients. The analyses were based on the data collected from one tertiary public hospital in Fujian province of China. We conducted interrupted time series analysis with a segmented regression model and multivariate analyses with a binary logistic regression model to analyze the impact of the government health insurance coverage on medicines utilization and the determinants of patient’s medication choice.

Results

The average proportion of patients who initiated medication with novel medicines increased from 37.4% before the government health insurance coverage to 69.2% afterwards. Such an increase was observed in all patient sub-groups. The monthly proportion of patients who initiated medication with novel medicines increased sharply by 18.3 % (95 %CI,10.4-34.0 %, p = 0.01) in September 2017, the afterwards trend continuously increased (95 %CI,1.03–3.60, p = 0.02). The critical determinants of patient's medication choice were mostly connected with the patient's health insurance benefits packages.

Conclusions

The government health insurance coverage of novel anti-breast-cancer medicines benefited the patients generally. The utilization of novel medicines such as trastuzumab continuously increased. The insurance coverage benefited well the patients in the high-risk age groups. However, rural patients, patients enrolled in the “resident program”, and patients from low-income residential areas and non-local patients benefited less from this policy. Improving the benefits package of the low-income patients and the “resident program” beneficiary would be of considerable significance for a more inclusive and equal health insurance coverage of novel anti-cancer medicines.
Value configurations for balancing standardization and customization in chronic care: a qualitative study
Authors: Colldén Christian , Hellström Andreas , Gremyr Ida
Published: August 2021

Background

Demands for both customization and standardization are increasing in healthcare. At the same time, resources are scarce, and healthcare managers are urged to improve efficiency. A framework of threevalue configurations– shop, chain, and network – has been proposed for how healthcare operations can be designed and organized for efficient value creation. In this paper, use of value configurations for balancing of standardization and customization is explored in the context of care for chronic mental conditions.

Methods

A typical case is presented to illustrate the manifestations of conflicting demands between customization and standardization, and the potential usefulness of the value configurations framework. Qualitative data were collected from managers and care developers in two focus groups and six semi-structured interviews, completed by a national document describing a care pathway. Data were coded and analysed using an insider-outsider approach.

Results

Operationalization of the balance between standardization and customization were found to be highly delegated and ad hoc. Also, the conflict between the two demands was often seen as aggravated by scarce resources. Value configurations can be fruitful as a means of discussing and redesigning care operations if applied at a suitable level of abstraction. Applied adequately, all three value configurations were recognized in the care operations for the patient group, with shop as the overarching configuration. Some opportunities for improved efficiency were identified, yet all configurations were seen as vital in the chronic care process.

Conclusions

The study challenges the earlier proposed organizational separation of care corresponding to different value configurations. Instead, as dual demand for customization and standardization permeates healthcare, parallel but explicated value configurations may be a path to improved quality and efficiency. Combined and intermediate configurations should also be further investigated.
Maternal education level and maternal healthcare utilization in the Democratic Republic of the Congo: an analysis of the multiple indicator cluster survey 2017/18
Authors: Wang Hanyu , Frasco Eric , Takesue Rie , Tang Kun
Published: August 2021

Background

Understanding how socioeconomic factors influence maternal health services utilization is crucial to reducing preventable maternal deaths in the DRC. Maternal education is considered an important associate of maternal health service utilization. This study aims to investigate the association between maternal education and the utilization of maternal health services, as well as present geographical and socio-economic disparities in the utilization.

Methods

The MICS survey was employed as the data source, which is a nationally representative survey conducted from 2017 to 2018 in the DRC. The exposure for this study was the maternal education level, which was categorized into three groups: (1) below primary and none, (2) primary and (3) secondary and above. Prenatal care indicators included: if the mother ever received prenatal care, if the mother had antenatal checks no less than four times, and if a skilled attendant was present at birth. Postnatal care indicators included: if the mother received postnatal care and if the baby was checked after birth. Emergency obstetric interventions were indicted by cesarean sections. Descriptive analyses and logistic regressions were used as analytical methods.

Results

Of all 8,560 participants included, 21.88 % had below primary school or no education, 39.81 % had primary school education, and 38.31 % had secondary education or above. The majority of participants were from rural areas, except for Kinshasa. Overall, a better education was associated with higher utilization of antenatal care. A dose-response effect was also observed. Compared to women with below primary or no education, women with secondary and above education were more likely to receive cesarean sections. Wealth status, as well as rural and urban division, modified the associations.

Conclusions

Mothers’ education level is an important associate for utilizing appropriate maternal healthcare, with wealth and region as modifying factors. Educational levels should be considered when designing public health interventions and women’s empowerment programs in the DRC. For example, relevant programs need to stratify the interventions according to educational attainment.
Regional variation of potentially avoidable hospitalisations in Switzerland: an observational study
Authors: Gygli Niklaus , Zúñiga Franziska , Simon Michael
Published: August 2021

Background

Primary health care is subject to regional variation, which may be due to unequal and inefficient distribution of services. One key measure of such variation are potentially avoidable hospitalisations, i.e., hospitalisations for conditions that could have been dealt with in situ by sufficient primary health care provision. Particularly, potentially avoidable hospitalisations for ambulatory care-sensitive conditions (ACSCs) are a substantial and growing burden for health care systems that require targeting in health care policy.

Aims

Using data from the Swiss Federal Statistical Office (SFSO) from 2017, we applied small area analysis to visualize regional variation to comprehensively map potentially avoidable hospitalisations for five ACSCs from Swiss nursing homes, home care organisations and the general population.

Methods

This retrospective observational study used data on all Swiss hospitalisations in 2017 to assess regional variations of potentially avoidable hospitalisations for angina pectoris, congestive heart failure, chronic obstructive pulmonary disease, diabetes complications and hypertension. We used small areas, utilisation-based hospital service areas (HSAs), and administrative districts (Cantons) as geographic zones. The outcomes of interest were age and sex standardised rates of potentially avoidable hospitalisations for ACSCs in adults (> 15 years). Our inferential analyses used linear mixed models with Gaussian distribution.

Results

We identified 46,479 hospitalisations for ACSC, or 4.3% of all hospitalisations. Most of these occurred in the elderly population for congestive heart failure and COPD. The median rate of potentially avoidable hospitalisation for ACSC was 527 (IQR 432–620) per 100.000 inhabitants. We found substantial regional variation for HSAs and administrative districts as well as disease-specific regional patterns.

Conclusions

Differences in continuity of care might be key drivers for regional variation of potentially avoidable hospitalisations for ACSCs. These results provide a new perspective on the functioning of primary care structures in Switzerland and call for novel approaches in effective primary care delivery.
Effect of organic and inorganic dietary selenium supplementation on gene expression in oviduct tissues and Selenoproteins gene expression in Lohman Brown-classic laying hens
Authors: Muhammad A. I. , Dalia A. M. , Loh T. C. , Akit H. , Samsudin A. A.
Published: August 2021

Background

The oviduct of a hen provides a conducive environment for egg formation, which needs a large amount of mineral elements from the blood via trans-epithelial permeability. Eggshell is the calcified layer on the outside of an egg that provides protection and is critical for egg quality. However, little is known about the genes or proteins involved in eggshell formation, and their relationship to dietary microminerals. We hypothesized that dietary selenium supplementation in chickens will influence genes involved in eggshell biomineralization, and improve laying hen antioxidant capacity. The objective of this research was to investigate how organic and inorganic dietary selenium supplementation affected mRNA expression of shell gland genes involved in eggshell biomineralization, and selenoproteins gene expression in Lohman Brown-Classic laying hens.

Results

Shell gland (Uterus) and liver tissue samples were collected from hens during the active growth phase of calcification (15–20 h post-ovulation) for RT-PCR analysis. In the oviduct (shell gland and magnum) and liver of laying hens, the relative expression of functional eggshell and hepatic selenoproteins genes was investigated. Results of qPCR confirmed the higher (p < 0.05) mRNA expression of OC-17 and OC-116 in shell gland of organic Se hen compared to inorganic and basal diet treatments. Similarly, dietary Se treatments affected the mRNA expression of OCX-32 and OCX-36 in the shell gland of laying hens. In the magnum, mRNA expression of OC-17 was significantly (p < 0.05) higher in hens fed-bacterial organic, while OC-116 mRNA expression was down-regulated in dietary Se supplemented groups compared to non-Se supplemented hens. Moreover, when compared to sodium selenite, only ADS18 bacterial Se showed significantly (p < 0.05) higher mRNA levels in GPX1, GPX4, DIO1, DIO2 and SELW1, while Se-yeast showed significantly (p < 0.05) higher mRNA levels in TXNRD1 than the non-Se group.

Conclusions

Dietary Se supplementation especially that from a bacterial organic source, improved shell gland and hepatic selenoproteins gene expression in laying hens, indicating that it could be used as a viable alternative source of Se in laying hens. The findings could suggest that organic Se upregulation of shell gland genes and hepatic selenoproteins in laying hens is efficient.
Rift Valley fever and Brucella spp. in ruminants, Somalia
Authors: Hassan-Kadle Ahmed A. , Osman Aamir M. , Shair Mohamed A. , Abdi Omar M. , Yusuf Abdulkarim A. , Ibrahim Abdalla M. , Vieira Rafael F. C.
Published: August 2021

Background

Fourteen-years after the last Rift Valley fever (RVF) virus (RVFV) outbreak, Somalia still suffers from preventable transboundary diseases. The tradition of unheated milk consumption and handling of aborted materials poses a public health risk for zoonotic diseases. Limited data are available on RVF and Brucella spp. in Somali people and their animals. Hence, this study has evaluated the occurrence of RVFV and Brucella spp. antibodies in cattle, goats and sheep sera from Afgoye and Jowhar districts of Somalia.

Methods

Serum samples from 609 ruminants (201 cattle, 203 goats and 205 sheep), were serologically screened for RVF by a commercial cELISA, and Brucella species by modified Rose Bengal Plate Test (mRBPT) and a commercial iELISA.

Results

Two out of 609 (0.3 %; 95 %CI: 0.04–1.2 %) ruminants were RVF seropositive, both were female cattle from both districts. Anti-Brucella spp. antibodies were detected in 64/609 (10.5 %; 95 %CI: 8.2–13.2 %) ruminants by mRBPT, which were 39/201 (19.4 %) cattle, 16/203 (7.9 %) goats and 9/205 (4.4 %) sheep. Cattle were 5.2 and 2.8 times more likely to be Brucella-seropositive than sheep (p = 0.000003) and goats (p = 0.001), respectively. When mRBPT-positive samples were tested by iELISA, 29/64 (45.3 %; 95 %CI: 32.8–58.3 %) ruminant sera were positive for Brucella spp. Only 23/39 (58.9 %) cattle sera and 6/16 (37.5 %) goat sera were positive to Brucella spp. by iELISA.

Conclusions

The present study showed the serological evidence of RVF and brucellosis in ruminants from Afgoye and Jowhar districts of Somalia. Considering the negligence of the zoonotic diseases at the human-animal interface in Somali communities, a One Health approach is needed to protect public health.
In-vitro and in-vivo comparisons of high versus low concentrations of inhaled epoprostenol to adult intubated patients
Authors: Li Jie , Augustynovich Ashley E. , Gurnani Payal K. , Fink James B.
Published: August 2021

Background

Inhaled epoprostenol (iEPO) has been shown to reduce pulmonary artery pressure and improve oxygenation. iEPO is mainly delivered via a syringe pump with feed tubing connected to a vibrating mesh nebulizer with high or low formulation concentration delivery.

Methods

An in vitro study and a two-period retrospective case–control study were implemented. The in vitro study compared iEPO delivery via invasive ventilation at low concentrations of 7.5, and 15 mcg/mL and high concentration at 30 mcg/mL, to deliver the ordered dose of 30 and 50 ng/kg/min for three clinical scenarios with predicted body weight of 50, 70 and 90 kg. While in the clinical study, adult patients receiving iEPO via invasive ventilation to treat refractory hypoxemia, pulmonary hypertension, or right ventricular failure were included. 80 patients received low concentration iEPO at multiple concentrations (2.5, 7.5, and 15 mcg/mL, depending on the ordered dose) from 2015 to 2017, while 84 patients received high concentration iEPO at 30 mcg/mL from 2018 to 2019.

Results

In the in vitro study, there were no significant differences in aerosol deposition between high vs low concentrations of iEPO at a dose of 50 ng/kg/min. In the clinical study, age, gender, ethnicity, and indications for iEPO were similar between high and low concentration groups. After 30–120 min of iEPO administration, both delivery strategies significantly improved oxygenation in hypoxemic patients and reduced mean pulmonary arterial pressure (mPAP) for patients with pulmonary hypertension. However, no significant differences of the incremental changes were found between two delivery groups. Compared to low concentration, high concentration delivery group had better adherence to the iEPO weaning protocol (96% vs 71%, p < 0.001), fewer iEPO syringes utilized per patient (5 [3, 10] vs 12 [6, 22], p = 0.001), and shorter duration of invasive ventilation (6 [3, 12] vs 9 [5, 18] days, p = 0.028). Intensive care unit length of stay and mortality were similar between two groups.

Conclusion

Compared to low concentration delivery of iEPO, high concentration iEPO via a vibrating mesh nebulizer maintained clinical benefits and increased clinician compliance with an iEPO weaning protocol, required less medication preparation time, and shortened duration of invasive ventilation.
Efficient expression of heterologous genes by the introduction of the endogenous glyceraldehyde-3-phosphate dehydrogenase gene intron 1 in Ganoderma lucidum
Authors: You Hao , Sun Bin , Li Na , Xu Jun-Wei
Published: August 2021

Background

Ganoderma lucidum, a well-known medicinal mushroom, has received wide attention as a promising cell factory for producing bioactive compounds. However, efficient expression of heterologous genes remains a major challenge in Ganoderma, hindering metabolic regulation research and molecular breeding of this species.

Results

We show that the presence of glyceraldehyde-3-phosphate dehydrogenase gene (gpd) intron 1 at the 5′ end of, the 3′ end of, or within the heterologous phosphinothricin-resistant gene (bar) is efficient for its expression in G. lucidum. The enhanced expression of bar is exhibited by the higher accumulation of mRNA and increased amounts of protein. Moreover, the insertion of the gpd intron 1 in the β-glucuronidase gene (gus) elevates its mRNA accumulation and enzyme activity, which facilitates the use of this reporter gene in Ganoderma.

Conclusions

This study has demonstrated the importance of the introduction of gpd intron 1 for the efficient expression of bar and gus in G. lucidum. The presence of the gpd intron 1 in heterologous genes increases levels of mRNA accumulation and protein expression in basidiomycete Ganoderma. The developed method may be utilized in upregulating the expression of other heterologous genes in Ganoderma.
Algal glycobiotechnology: omics approaches for strain improvement
Authors: Sirohi Ranjna , Joun Jaemin , Choi Hong II , Gaur Vivek Kumar , Sim Sang Jun
Published: August 2021

Microalgae has the capability to replace petroleum-based fuels and is a promising option as an energy feedstock because of its fast growth, high photosynthetic capacity and remarkable ability to store energy reserve molecules in the form of lipids and starch. But the commercialization of microalgae based product is difficult due to its high processing cost and low productivity. Higher accumulation of these molecules may help to cut the processing cost. There are several reports on the use of various omics techniques to improve the strains of microalgae for increasing the productivity of desired products. To effectively use these techniques, it is important that the glycobiology of microalgae is associated to omics approaches to essentially give rise to the field of algal glycobiotechnology. In the past few decades, lot of work has been done to improve the strain of various microalgae such as Chlorella, Chlamydomonas reinhardtii, Botryococcus braunii etc., through genome sequencing and metabolic engineering with major focus on significantly increasing the productivity of biofuels, biopolymers, pigments and other products. The advancements in algae glycobiotechnology have highly significant role to play in innovation and new developments for the production algae-derived products as above. It would be highly desirable to understand the basic biology of the products derived using -omics technology together with biochemistry and biotechnology. This review discusses the potential of different omic techniques (genomics, transcriptomics, proteomics, metabolomics) to improve the yield of desired products through algal strain manipulation.
OIP5-AS1 contributes to the development in endometrial carcinoma cells by targeting miR-152-3p to up-regulate SLC7A5
Authors: Liang Minglin , Wang Hongbo , Liu Cong , Lei Tao , Min Jie
Published: August 2021

Background

Endometrial carcinoma (EC) is one common gynecological tumor, threatening physical and psychological health of females. Huge amount of essays indicated that long non-coding RNAs (lncRNAs) were widely reported to serve as a crucial regulator in the biological movements among multiple carcinomas, including EC.

Methods

RT-qPCR was implemented to detect the expression of target genes. Loss/gain-of-function experiments certified the impacts of OIP5-AS1 and miR-152-3p on EC cell progression.

Results

Data of this research suggested that powerful expression of OIP5-AS1 was discovered in EC cell lines. Loss/gain-of-function assays inferred that OIP5-AS1 promoted proliferative, migratory and invasive abilities, and Epithelial-Mesenchymal Transition (EMT). In addition, we identified miR-152-3p expression was negatively modulated by OIP5-AS1. OIP5-AS1 accelerated the development of EC cells via downregulating miR-152-3p expression. SLC7A5 was selected out as a downstream target of miR-152-3p. The competing relationship between OIP5-AS1 and SLC7A5 was corroborated by luciferase reporter assay. Eventually, the results of rescue assays indicated that SLC7A5 overexpression could restore the impacts of OIP5-AS1 ablation on the progression of EC cells.

Conclusion

Our research confirmed that OIP5-AS1 propeled the development of EC cells through targeting miR-152-3p/SLC7A5. OIP5-AS1 could be utilized as a target for EC treatment.
LPCAT1 overexpression promotes the progression of hepatocellular carcinoma
Authors: He Rong-Quan , Li Jian-Di , Du Xiu-Fang , Dang Yi-Wu , Yang Lin-Jie , Huang Zhi-Guang , Liu Li-Min , Liao Liu-Feng , Yang Hong , Chen Gang
Published: August 2021

Background

Hepatocellular carcinoma (HCC) remains one of the most common malignant neoplasms. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role in the lipid remodelling and is correlated with various neoplasms. Nonetheless, the biological functions and molecular mechanisms of LPCAT1 underlying HCC remain obscure.

Methods

In the present study, we investigated the role of LPCAT1 in the progression of HCC. In-house RT-qPCR, tissue microarrays, and immunohistochemistry were performed to detect the expression levels and the clinical value of LPCAT1 in HCC. External datasets were downloaded to confirm the results. Proliferation, migration, invasiveness, cell cycle, and apoptosis assays were conducted to reveal the biological effects LPCAT1 has on SMMC-7721 and Huh7 cells. HCC differentially expressed genes and LPCAT1 co-expressed genes were identified to explore the molecular mechanisms underlying HCC progression.

Results

LPCAT1 showed upregulated expression in 3715 HCC specimens as opposed to 3105 non-tumour specimens. Additionally, LPCAT1 might be an independent prognostic factor for HCC. LPCAT1-knockout hampered cellular proliferation, migration, and metastasis in SMMC-7721 and Huh7 cells. More importantly, the cell cycle and chemical carcinogenesis were the two most enriched signalling pathways.

Conclusions

The present study demonstrated that increased LPCAT1 correlated with poor prognosis in HCC patients and fuelled HCC progression by promoting cellular growth, migration, and metastasis.
The impact of impaired DNA mobility on gene electrotransfer efficiency: analysis in 3D model
Authors: Meglič Saša Haberl , Pavlin Mojca
Published: August 2021

Background

Gene electrotransfer is an established method that enables transfer of DNA into cells with electric pulses. Several studies analyzed and optimized different parameters of gene electrotransfer, however, one of main obstacles toward efficient electrotransfection in vivo is relatively poor DNA mobility in tissues. Our aim was to analyze the effect of impaired mobility on gene electrotransfer efficiency experimentally and theoretically. We applied electric pulses with different durations on plated cells, cells grown on collagen layer and cells embedded in collagen gel (3D model) and analyzed gene electrotransfer efficiency. In order to analyze the effect of impaired mobility on gene electrotransfer efficiency, we applied electric pulses with different durations on plated cells, cells grown on collagen layer and cells embedded in collagen gel (3D model) and analyzed gene electrotransfer efficiency.

Results

We obtained the highest transfection in plated cells, while transfection efficiency of embedded cells in 3D model was lowest, similarly as in in vivo. To further analyze DNA diffusion in 3D model, we applied DNA on top or injected it into 3D model and showed, that for the former gene electrotransfer efficiency was similarly as in in vivo. The experimental results are explained with theoretical analysis of DNA diffusion and electromobility.

Conclusion

We show, empirically and theoretically that DNA has impaired electromobility and especially diffusion in collagen environment, where the latter crucially limits electrotransfection. Our model enables optimization of gene electrotransfer in in vitro conditions.
Human detection thresholds of DC, AC, and hybrid electric fields: a double-blind study
Authors: Kursawe Michael , Stunder Dominik , Krampert Thomas , Kaifie Andrea , Drießen Sarah , Kraus Thomas , Jankowiak Kathrin
Published: August 2021

Background

In the course of the ongoing transition of electric energy systems, transmission corridors are often upgraded to higher voltages and other technologies leading to another quality of human exposure. The study aims to determine human detection thresholds for direct current (DC), alternating current (AC), and hybrid electric fields (various DC; constant AC).

Methods

A total of 203 participants were exposed to DC, AC, and hybrid electric fields (EFs) in a highly specialized whole-body exposure laboratory using a double-blind experimental setting. Additionally, the participants were exposed to ion currents in part of the DC and hybrid sessions. To investigate environmental influences, relative humidity was changed in two subgroups during EF perception. Methods derived from the signal detection theory and the adaptive staircase procedure based on the single interval adjustment matrix were used to assess individual sensitivity and detection thresholds, respectively.

Results

The results indicated that detection thresholds of hybrid EF were lower compared to single EF presentation of DC or AC. Ion current exposure enhanced EF perception. High relative humidity facilitated DC EF perception, whereas low relative humidity reinforced the perception of AC EFs.

Conclusions

With this systematic investigation of human perception of DC, AC, and hybrid EFs, detection thresholds were provided, which can help improve the construction processes of energy transmission systems and the prevention of unwanted sensory perception by contributing to the determination of limit values.
Effect of ZnO nanoparticles on methicillin, vancomycin, linezolid resistance and biofilm formation in Staphylococcus aureus isolates
Authors: Abdelraheem Wedad M. , Khairy Rasha M. M. , Zaki Alaa I. , Zaki Shaimaa H.
Published: August 2021

Background

Multidrug resistant (MDR) and biofilm producing Staphylococcus aureus strains are usually associated with serious infections. This study aimed to evaluate the antibacterial and antibiofilm-formation effects of zinc oxide nanoparticles (ZnO-NPs) against staphylococcus aureus (S. aureus) isolates.

Methods

A total of 116 S. aureus isolates were recovered from 250 burn wound samples. The antimicrobial/antibiofilm effects of ZnO-NPs against methicillin, vancomycin and linezolid resistant S. aureus (MRSA, VRSA and LRSA) isolates were examined using phenotypic and genotypic methods. The minimum inhibitory concentration (MIC) of ZnO-NPs was determined by microdilution method. The effects of sub-MIC concentrations of ZnO-NPs on biofilm formation and drug resistance in S. aureus were determined by the microtiter plate method. The change in the expression levels of the biofilm encoding genes and resistance genes in S. aureus isolates after treatment with ZnO-NPs was assessed by real time reverse transcriptase PCR (rt-PCR).

Results

MICs of ZnO-NPs in S. aureus isolates were (128–2048 µg/ml). The sub-MIC of ZnO-NPs significantly reduced biofilm formation rate (the highest inhibition rate was 76.47% at 1024  µg/ml) and the expression levels of biofilm genes (ica A, ica D and fnb A) with P < 0.001. Moreover, Sub-MIC of ZnO-NPs significantly reduced the rates of MRSA from 81.9 (95 isolates) to 13.30% (15 isolates), VRSA from 33.60 (39 isolates) to 0% and LARSA from 29.30 (34) to 0% as well as the expression levels of resistance genes (mec A, van A and cfr) with P value < 0.001.

Conclusion

ZnO-NPs can be used as antibiofilm and potent antimicrobial against MRSA, VRSA and LRSA isolates.
RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment
Authors: Park Han-Hee , Kim Hwa-Ryeon , Park Sang-Yeong , Hwang Sung-Min , Hong Sun Mi , Park Sangwook , Kang Ho Chul , Morgan Michael J. , Cha Jong-Ho , Lee Dakeun , Roe Jae-Seok , Kim You-Sun
Published: August 2021

Background

Necroptosis is emerging as a new target for cancer immunotherapy as it is now recognized as a form of cell death that increases tumor immunogenicity, which would be especially helpful in treating immune-desert tumors. De novo synthesis of inflammatory proteins during necroptosis appears especially important in facilitating increased anti-tumor immune responses. While late-stage transcription mediated by NF-κB during cell death is believed to play a role in this process, it is otherwise unclear what cell signaling events initiate this transactivation of inflammatory genes.

Methods

We employed tandem-affinity purification linked to mass spectrometry (TAP-MS), in combination with the analysis of RNA-sequencing (RNA-Seq) datasets to identify the Tripartite Motif Protein 28 (TRIM28) as a candidate co-repressor. Comprehensive biochemical and molecular biology techniques were used to characterize the role of TRIM28 in RIPK3 activation-induced transcriptional and immunomodulatory events. The cell composition estimation module was used to evaluate the correlation between RIPK3/TRIM28 levels and CD8+ T cells or dendritic cells (DC) in all TCGA tumors.

Results

We identified TRIM28 as a co-repressor that regulates transcriptional activity during necroptosis. Activated RIPK3 phosphorylates TRIM28 on serine 473, inhibiting its chromatin binding activity, thereby contributing to the transactivation of NF-κB and other transcription factors, such as SOX9. This leads to elevated cytokine expression, which then potentiates immunoregulatory processes, such as DC maturation. The expression of RIPK3 has a significant positive association with the tumor-infiltrating immune cells populations in various tumor type, thereby activating anti-cancer responses.

Conclusion

Our data suggest that RIPK3 activation-dependent derepression of TRIM28 in cancer cells leads to increased immunostimulatory cytokine production in the tumor microenvironment, which then contributes to robust cytotoxic anti-tumor immunity.
Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis
Authors: Rong Zeyin , Shi Si , Tan Zhen , Xu Jin , Meng Qingcai , Hua Jie , Liu Jiang , Zhang Bo , Wang Wei , Yu Xianjun , Liang Chen
Published: August 2021

Background

Extensive studies have demonstrated the pivotal roles of circular RNAs (circRNAs) in the occurrence and development of different human cancers. However, the expression and regulatory roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear.

Methods

CircEYA3 was explored based on Gene Expression Omnibus (GEO) dataset analysis. qRT-PCR was applied to determine the expression of circRNAs, miRNAs and mRNAs in PDAC cells and tissues. The biological roles of circEYA3 in vitro and in vivo were determined by performing a series of functional experiments. Further, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA pull-down assays, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of circEYA3 with miR-1294.

Results

CircEYA3 was elevated in PDAC tissues and cells, and a higher level of circEYA3 was significantly associated with a poorer prognosis in patients with PDAC. Functionally, circEYA3 increased energy production via ATP synthesis to promote PDAC progression in vitro and in vivo. Mechanistically, circEYA3 functions as an endogenous miR-1294 sponge to elevate c-Myc expression, thus exerting its oncogenic functions.

Conclusion

CircEYA3 promotes the progression of PDAC through the miR-1294/c-Myc signalling axis, and circEYA3 may be an efficient molecular therapeutic target in PDAC.
Circulating retinol binding protein 4 levels in coronary artery disease: a systematic review and meta-analysis
Authors: Chen Hengying , Zhang Jiaying , Lai Jiayu , Zhou Yingyu , Lin Xiaoping , Deng Guifang , Zhang Zheqing , Li Liping
Published: August 2021

Background

Retinol binding protein 4 (RBP4) has been proposed to play a role in the pathophysiology of coronary artery disease (CAD), but previous findings on the association of RBP4 levels with CAD are inconsistent.

Methods

A meta-analysis based on observational studies was conducted to evaluate the association between circulating RBP4 levels and CAD. Databases including PubMed, Web of Science, Embase, Google Scholar and ClinicalTrials.gov database were searched for eligible studies published up to 12 July 2021. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using the inverse variance heterogeneity (IVhet) and random-effects model for data with moderate and high heterogeneity (I2 > 30%) and data with low heterogeneity were analysed using a fixed-effects model (I2 ≤ 30%). Moreover, a bias-adjusted quality-effects model was generated, and the prediction interval was also calculated under the random-effects model.

Results

Two nested case-control studies, one cohort study and twelve case–control studies with a total of 7111 participants were included. Circulating RBP4 levels in patients with CAD were comparable to those in the controls under the IVhet model (SMD: 0.25, 95% CI: − 0.29-0.79, I2: 96.00%). The quality-effects model produced consistent results. However, the association turned to be significant under the random-effect model (SMD: 0.46, 95% CI: 0.17–0.75, I2: 96.00%), whereas the 95% predictive interval (PI) included null values (95% PI: − 0.82-1.74). Subgroup analyses illustrated a positive relationship between CAD and RBP4 levels in patients with complications (SMD: 1.34, 95% CI: 0.38–2.29, I2: 96.00%). The meta-regression analysis revealed that the mean BMI of patients (P = 0.03) and complication status (P = 0.01) influenced the variation in SMD.

Conclusions

There was low-quality evidence that patients with CAD exhibited similar circulating RBP4 levels compared with controls, and high inter-study heterogeneity was also observed. Thus, RBP4 might not be a potential risk factor for CAD. Comparisons among different subtypes of RBP4 with larger sample size are needed in the future.
Tetraspanins are unevenly distributed across single extracellular vesicles and bias sensitivity to multiplexed cancer biomarkers
Authors: Mizenko Rachel R. , Brostoff Terza , Rojalin Tatu , Koster Hanna J. , Swindell Hila S. , Leiserowitz Gary S. , Wang Aijun , Carney Randy P.
Published: August 2021

Background

Tetraspanin expression of extracellular vesicles (EVs) is often used as a surrogate for their detection and classification, a practice that typically assumes their consistent expression across EV sources.

Results

Here we demonstrate that there are distinct patterns in colocalization of tetraspanin expression of EVs enriched from a variety of in vitro and in vivo sources. We report an optimized method for the use of single particle antibody-capture and fluorescence detection to identify subpopulations according to tetraspanin expression and compare our findings with nanoscale flow cytometry. We found that tetraspanin profile is consistent from a given EV source regardless of isolation method, but that tetraspanin profiles are distinct across various sources. Tetraspanin profiles measured by flow cytometry do not totally agree, suggesting that limitations in subpopulation detection significantly impact apparent protein expression. We further analyzed tetraspanin expression of single EVs captured non-specifically, revealing that tetraspanin capture can bias the apparent multiplexed tetraspanin profile. Finally, we demonstrate that this bias can have significant impact on diagnostic sensitivity for tumor-associated EV surface markers.

Conclusion

Our findings may reveal key insights into protein expression heterogeneity of EVs that better inform EV capture and detection platforms for diagnostic or other downstream use.

Graphical abstract
RVG-functionalized reduction sensitive micelles for the effective accumulation of doxorubicin in brain
Authors: Xu Jiangkang , Yang Xiaoye , Ji Jianbo , Gao Yuan , Qiu Na , Xi Yanwei , Liu Anchang , Zhai Guangxi
Published: August 2021

Background

Glioblastoma is a lethal neoplasm with few effective therapy options. As a mainstay in the current treatment of glioma at present, chemotherapeutic agents usually show inadequate therapeutic efficiency due to their low blood brain barrier traversal and brain targeting, together with tumor multidrug resistance. Novel treatment strategies are thus urgently needed to improve chemotherapy outcomes.

Results

Here, we report that nanomedicines developed by functionalizing the neurotropic rabies virus-derived polypeptide, RVG, and loading reduction-sensitive nanomicelles (polymer and doxorubicin) enable a highly specific and efficacious drug accumulation in the brain. Interestingly, curcumin serves as the hydrophobic core of the polymer, while suppressing the major efflux proteins in doxorubicin-resistant glioma cells. Studies on doxorubicin-resistant rat glioma cells demonstrate that the RVG-modified micelles exhibit superior cell entry and antitumor activity. In vivo research further showed that RVG modified nanomicelles significantly enhanced brain accumulation and tumor inhibition rate in mice, leading to a higher survival rate with negligible systemic toxicity. Moreover, effective suppression of recurrence and pulmonary metastatic nodules were also determined after the RVG-modified nanomicelles treatment.

Conclusions

The potential of RVG-modified nanomicelles for glioma was demonstrated. Brain accumulation was markedly enhanced after intravenous administration. This unique drug delivery nanoplatform to the brain provides a novel and powerful therapeutic strategy for the treatment of central nervous system disorders including glioma.

Graphic abstract
Health-related quality of life in a general population sample in Kazakhstan and its sociodemographic and occupational determinants
Authors: Vinnikov Denis , Raushanova Aizhan , Romanova Zhanna , Tulekov Zhangir
Published: August 2021

Background

Health-related quality of life (HRQL) in the general population of Kazakhstan has never been characterized. We constructed this population-based study of the largest city in Kazakhstan, Almaty with the aim to quantitatively assess HRQL and ascertain whether occupation and lifestyle are associated with HRQL in this population.

Methods

In a random sample (N = 1500) of general population in Almaty (median age 49 (interquartile range 28) years, 50% women), we collected data on demographics, socioeconomic status, lifestyle, lifetime occupational history and general HRQL using SF-8 instrument. The association of demographic and occupational predictors with HRQL was tested in multiple regression models.

Results

No occupational associations were found for physical component score in the models adjusted for age, sex, income, cigarette and waterpipe smoking, electronic cigarette use, physical activity, alcohol and exposure to secondhand smoke. Ever being a manager (β − 1.63 (95% confidence interval (CI) − 2.92; − 0.34)), a welder (β − 5.11 (95% CI − 8.77; − 1.46)) and a secretary (β − 5.06 (95% CI − 8.56; − 1.56)) for one year or more was associated with poorer mental component score in the models adjusted for age, sex, income, cigarette smoking, physical activity and each other. Age, income and physical activity were independent predictors of both physical and mental components.

Conclusions

Occupational history is associated with HRQL in the general population in Almaty, Kazakhstan, but the mechanism explaining this association should be further elucidated.
Clinical application of gelatin sponge microparticles combined with pirarubicin for hepatic transcatheter arterial chemoembolization in breast cancer liver metastasis treatment: results of a single-center long-term study
Authors: Zhao Guang Sheng , Liu Song , Liu Ying , Ma Jian , Wang Ruo Yu , Bian Jie , Zhou Jun , Wu Jian Lin , Zhang Yue Wei
Published: August 2021

Objective

To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM).

Methods

Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed.

Results

By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant.

Conclusions

The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.
Identification and verification of HCAR3 and INSL5 as new potential therapeutic targets of colorectal cancer
Authors: Yang Xuan , Wei Wangao , Tan Shisheng , Guo Linrui , Qiao Song , Yao Biao , Wang Zi
Published: August 2021

Background

Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines.

Methods

A series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein–protein interaction (PPI) network. This analysis enabled the identification of Hub genes, for which the mRNA expression and overall survival of CRC patients data distribution was explored in The Cancer Genome Atlas (TCGA) colon cancer and rectal cancer (COADREAD) database. Furthermore, the differential expression of HCAR3 and INLS5 was validated in clinical tumor samples by Real-time quantitative PCR analysis, western blotting analysis, and immunohistochemistry analysis. Finally, CRC cells over-expressing INSL5 were constructed and used for CCK8, cell cycle, and cell apoptosis validation assays in vitro.

Results

A total of 286 differentially expressed genes (DEGs) were screened, including 64 genes with increased expression and 143 genes with decreased expression in 2 CRC database, from which 10 key genes were identified: CXCL1, HCAR3, CXCL6, CXCL8, CXCL2, CXCL5, PPY, SST, INSL5, and NPY1R. Among these genes, HCAR3 and INSL5 had not previously been explored and were further verified in vitro.

Conclusions

HCAR3 expression was higher in CRC tissues and associated with better overall survival of CRC patients. INSL5 expression in normal tissue was higher than that in tumor tissue and its high expression was associated with a better prognosis for CRC. The overexpression of INSL5 significantly inhibited the proliferation and promoted the shearing of PARP of CRC cells. This integrated bioinformatics study presented 10 key hub genes associated with CRC. HCAR3 and INSL5 were expressed in tumor tissue and these were associated with poor survival and warrant further studies as potential therapeutic targets.
The physiotherapy workforce in the Brazilian Unified Health Care System
Authors: Rodés Carolina Hart , Daré João Vitor Lovato , de Araujo Bruna Carolina , Graciani Leonardo , João Silvia Maria Amado , Germani Ana Claudia Camargo Gonçalves , Schmitt Ana Carolina Basso
Published: August 2021

Background

Maintaining sufficient health care workforce is a global priority to achieve universal health coverage. Therefore this study addresses the availability of physiotherapists in Brazil.

Objective

To describe secular trends of the physiotherapy workforce-to-population ratio in the Unified Health System, considering public and private sector and care level (primary, secondary, tertiary) in Brazil and its regions.

Method

Descriptive exploratory quantitative study based on secondary sources. All data related to the distribution of physiotherapists between August 2007 and September 2016 regarding facilities types, location and public and private sectors was obtained from the Brazilian National Registry of Health Care Facilities. Data related to the population of Brazil was extracted from Brazilian Institute of Geography and Statistics. The physiotherapy workforce-to-population ratio was calculated by the number of physiotherapists per 1000 population (public and private sector and care level) by ANOVA test. The distribution trends are represented on maps. Annual growth rates were estimated with Prais–Winsten linear regression models, with a significance level of 0.05, autocorrelation was checked by the Durbin–Watson test.

Results

The physiotherapists ratio in Brazil was 0.22/1000 population in 2007 and 0.41 in 2016, showing growth of 86%, with an increasing trend of 0.5% on an annual average. The public sector had the biggest physiotherapy workforce in the country in 2007 and 2016. The primary health care had the smallest physiotherapy workforce-to-population ratio (2007: p > 0.001 and 2016: p = 0.003), even though it had the largest growth trend in annual average (0.9% p > 0.001), followed by public and private tertiary health care sectors (0.8% p > 0.001). The workforce in secondary health care was bigger in the private sector than in the public sector (0.6% p > 0.001 vs. 0.2% p = 0.004). Overall, all regions had greater growth of physiotherapy workforce-to-population ratio in public primary and tertiary health care sectors, and private secondary health care sector, mainly the Southeast, South and Central-West regions.

Conclusion

Although the physiotherapy workforce in Brazil is relatively small, there was a trend towards growth with differences among care levels, and public and private sectors. The physiotherapy workforce-to-population ratio is bigger in the private secondary health care sector, followed by public tertiary, secondary and primary health care sectors. Sub-national regions show similar trends to the national estimates, with minor variations by region.