bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving access to medicines for non-communicable diseases in rural primary care: results from a quasi-randomized cluster trial in a district in South India
Authors: Pati Manoj Kumar , Bhojani Upendra , Elias Maya Annie , Srinivas Prashanth N. 
Published: August 2021

Abstract
Background
A large proportion of non-communicable diseases (NCDs) are treatable within primary health care (PHC) settings in a cost-effective manner. However, the utilization of PHCs for NCD care is comparatively low in India. The Access-to-Medicines (ATM) study examined whether (and how) interventions aimed at health service optimization alone or combined with community platform strengthening improve access to medicines at the primary health care level within the context of a local health system.

Method
A quasi-randomized cluster trial was used to assess the effectiveness of the intervention (18 months) implemented across 39 rural PHCs (clusters) of three sub-districts of Tumkur in southern India. The intervention was allocated randomly in a 1:1:1 sequence across PHCs and consisted of three arms: Arm A with a package of interventions aimed at health service delivery optimization; B for strengthening community platforms in addition to A; and the control arm. Group allocation was not blinded to providers and those who assessed outcomes. A household survey was used to understand health-seeking behaviour, access and out-of-pocket expenditure (OOP) on key anti-diabetic and anti-hypertension medicines among patients; facility surveys were used to assess the availability of medicines at PHCs. Primary outcomes of the study are the mean number of days of availability of antidiabetic and antihypertensive medicines at PHCs, the mean number of patients obtaining medicines from PHC and OOP expenses.

Result
The difference-in-difference estimate shows a statistically insignificant increase of 31.5 and 11.9 in mean days for diabetes and hypertension medicines availability respectively in the study arm A PHCs beyond the increase in the control arm. We further found that there was a statistically insignificant increase of 2.2 and 3.8 percentage points in the mean proportion of patients obtaining medicines from PHC in arm A and arm B respectively, beyond the increase in the control arm.

Conclusion
There were improvements in NCD medicine availability across PHCs, the number of patients accessing PHCs and reduction in OOP expenditure among patients, across the study arms as compared to the control arm; however, these differences were not statistically significant.

Trial registration
Trial registration number CTRI/2015/03/005640. This trial was registered on 17/03/2015 in the Clinical Trial Registry of India (CTRI) after PHCs were enrolled in the study (retrospectively registered). The CTRI is the nodal agency of the Indian Council of Medical Research for registration of all clinical, experimental, field intervention and observation studies.
A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome with diabetes and the choices of the appropriate hypoglycemic drugs: a case report
Authors: Liu Zhiying , Wang Sai , Zhang Ruixiao , Wang Cui , Lu Jingru , Shao Leping 
Published: August 2021

Abstract
Background
Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. It is universally known that both hypokalemia and hypomagnesemia can influence insulin secretion and insulin resistance, but the exact mechanisms require further study. We identified a novel deletion variant of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes.

Case presentation
A 55-year-old diabetic female patient was hospitalized for evaluation because of paroxysmal general weakness and numbness of extremities for one year. We suspected that she was suffering from GS by initial estimation. Direct Sanger sequencing was used to analyze the causative gene SLC12A3 of GS. Oral glucose tolerance test (OGTT) was carried out to assess the glucose metabolism and insulin resistance status. Genetic analysis revealed that she was a compound heterozygote for a recurrent missense mutation c.179C > T and a novel deletion c.1740delC in SLC12A3, thus her diagnosis of GS was confirmed. The patient was treated with potassium chloride (3.0 g/d) and magnesium chloride (element magnesium 350 mg/d) on the basis of initial treatment of diabetes with hypoglycemic drug (Repaglinide, 3.0 mg/day). However, she developed frequent hypoglycemia after one week. OGTT showed that her glucose metabolism and insulin resistance much improved after potassium and magnesium supplemental therapy. Then we changed the hypoglycemic agent to a dipeptidyl peptidase-4 (DPP-4) inhibitor (Trajenta 5 mg/d), since then her blood glucose level remained normal during two-year of follow-up.

Conclusion
We have identified a novel deletion of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. We suggested that attention need to be paid to blood glucose monitoring in GS patients, especially when hypokalemia and hypomagnesemia are corrected. Besides, the insufficient blood volume and serum electrolyte disturbance should also be taken into consideration in the selecting hypoglycemic drugs for GS patients.
Development and optimization of a microbial co-culture system for heterologous indigo biosynthesis
Authors: Chen Tingting , Wang Xiaonan , Zhuang Lei , Shao Alan , Lu Yinghua , Zhang Haoran 
Published: August 2021

Abstract
Background
Indigo is a color molecule with a long history of being used as a textile dye. The conventional production methods are facing increasing economy, sustainability and environmental challenges. Therefore, developing a green synthesis method converting renewable feedstocks to indigo using engineered microbes is of great research and application interest. However, the efficiency of the indigo microbial biosynthesis is still low and needs to be improved by proper metabolic engineering strategies.

Results
In the present study, we adopted several metabolic engineering strategies to establish an efficient microbial biosynthesis system for converting renewable carbon substrates to indigo. First, a microbial co-culture was developed using two individually engineered E. coli strains to accommodate the indigo biosynthesis pathway, and the balancing of the overall pathway was achieved by manipulating the ratio of co-culture strains harboring different pathway modules. Through carbon source optimization and application of biosensor-assisted cell selection circuit, the indigo production was improved significantly. In addition, the global transcription machinery engineering (gTME) approach was utilized to establish a high-performance co-culture variant to further enhance the indigo production. Through the step-wise modification of the established system, the indigo bioproduction reached 104.3 mg/L, which was 11.4-fold higher than the parental indigo producing strain.

Conclusion
This work combines modular co-culture engineering, biosensing, and gTME for addressing the challenges of the indigo biosynthesis, which has not been explored before. The findings of this study confirm the effectiveness of the developed approach and offer a new perspective for efficient indigo bioproduction. More broadly, this innovative approach has the potential for wider application in future studies of other valuable biochemicals’ biosynthesis.
Characterization of three glutamate decarboxylases from Bacillus spp. for efficient γ-aminobutyric acid production
Authors: Sun Lei , Bai Yingguo , Zhang Xiu , Zhou Cheng , Zhang Jie , Su Xiaoyun , Luo Huiying , Yao Bin , Wang Yuan , Tu Tao 
Published: August 2021

Abstract
Background
Gamma-aminobutyric acid (GABA) is an important bio-product used in pharmaceuticals and functional foods and as a precursor of the biodegradable plastic polyamide 4. Glutamate decarboxylase (GAD) converts l-glutamate (l-Glu) into GABA via decarboxylation. Compared with other methods, develop a bioconversion platform to produce GABA is of considerable interest for industrial use.

Results
Three GAD genes were identified from three Bacillus strains and heterologously expressed in Escherichia coli BL21 (DE3). The optimal reaction temperature and pH values for three enzymes were 40 °C and 5.0, respectively. Of the GADs, GADZ11 had the highest catalytic efficiency towards l-Glu (2.19 mM− 1 s− 1). The engineered E. coli strain that expressed GADZ11 was used as a whole-cell biocatalyst for the production of GABA. After repeated use 14 times, the cells produced GABA with an average molar conversion rate of 98.6% within 14 h.

Conclusions
Three recombinant GADs from Bacillus strains have been conducted functional identification. The engineered E. coli strain heterologous expressing GADZ1, GADZ11, and GADZ20 could accomplish the biosynthesis of l-Glu to GABA in a buffer-free reaction at a high l-Glu concentration. The novel engineered E. coli strain has the potential to be a cost-effective biotransformation platform for the industrial production of GABA.
CircFAM13B promotes the proliferation of hepatocellular carcinoma by sponging miR-212, upregulating E2F5 expression and activating the P53 pathway
Authors: Xie Ying , Hang Xiaofeng , Xu Wensheng , Gu Jing , Zhang Yuanjing , Wang Jianrong , Zhang Xiucui , Cao Xinghao , Zhan Junjie , Wang Junxue , Gan Jianhe 
Published: August 2021

Abstract
Background
Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered.

Methods
In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo.

Results
We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells.

Conclusions
Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.
Coverage, determinants of use and repurposing of long-lasting insecticidal nets two years after a mass distribution in Lihir Islands, Papua New Guinea: a cross-sectional study
Authors: Millat-Martínez Pere , Gabong Rebecca , Balanza Núria , Luana Sakaia , Sanz Sergi , Raulo Silvia , Elizah Arthur , Wali Chilaka , Paivu Benjamin , Dalmas Julian , Tabie Samson , Karl Stephan , Laman Moses , Pomat William , Mitjà Oriol , Baro Bàrbara , Bassat Quique 
Published: August 2021

Abstract
Background
Universal coverage with long-lasting insecticidal nets (LLINs) is an essential component of malaria control programmes. Three-yearly mass distribution of LLINs in Papua New Guinea (PNG) has been successful in reducing infection transmission since 2009, but malaria prevalence ramped up from 2015 onwards. Although LLIN universal coverage is mostly achieved during these campaigns, it may not be related with net use over time. Uses given to LLINs and non-compliance of this strategy were evaluated.

Methods
A knowledge, attitude and practice (KAP) cross-sectional study was conducted in Lihir Islands, PNG, 2–2.5 years after the last LLIN mass distribution campaign. Data on bed net ownership, use and maintenance behaviour was collected using a household questionnaire administered by trained community volunteers. Logistic regression models were used to identify factors associated with owning at least one LLIN and sleeping under a LLIN the previous night.

Results
Among 2694 households surveyed, 27.4 % (95 % CI: 25.8–29.2) owned at least one LLIN and 8.7 % (95 % CI: 7.6–9.8) had an adequate LLIN coverage (at least one LLIN for every two people). Out of 13,595 individuals in the surveyed households, 13.6 % (95 % CI: 13.0-–4.2) reported having slept under a LLIN the preceding night. Determinants for sleeping under LLIN included living in a household with adequate LLIN coverage [adjusted OR (aOR) = 5.82 (95 % CI: 3.23–10.49)], household heads knowledge about LLINs [aOR = 16.44 (95 % CI: 8.29–32.58)], and female gender [aOR = 1.92 (95 % CI: 1.53–2.40)] (all p-values < 0.001). LLIN use decreased with older age [aOR = 0.29 (95 % CI: 0.21–0.40) for ≥ 15 year-olds, aOR = 0.38 (95 % CI: 0.27–0.55) for 5–14 year-olds] compared to < 5 year-olds (p-value < 0.001). Knowledge on the use of LLIN was good in 37.0 % of the household heads. Repurposed nets were reported serving as fishing nets (30.4 %), fruits and seedlings protection (26.6 %), covering up food (19.0 %) and bed linen (11.5 %).

Conclusions
Two years after mass distribution, LLIN coverage and use in Lihir Islands is extremely low. Three yearly distribution campaigns may not suffice to maintain an acceptable LLIN coverage unless knowledge on maintenance and use is promoted trough educational campaigns.
Thymoquinone loading into hydroxyapatite/alginate scaffolds accelerated the osteogenic differentiation of the mesenchymal stem cells
Authors: Rahmani-Moghadam Ebrahim , Talaei-Khozani Tahereh , Zarrin Vahideh , Vojdani Zahra 
Published: August 2021

Abstract
Background
Phytochemical agents such as thymoquinone (TQ) have osteogenic property. This study aimed to investigate the synergic impact of TQ and hydroxyapatite on mesenchymal stem cell differentiation. Alginate was also used as drug vehicle.

Methods
HA scaffolds were fabricated by casting into polyurethane foam and sintering at 800 °C, and then, 1250 °C and impregnated by TQ containing alginate. The adipose-derived stem cells were aliquoted into 4 groups: control, osteogenic induced-, TQ and osteogenic induced- and TQ-treated cultures. Adipose derived-mesenchymal stem cells were mixed with alginate and loaded into the scaffolds

Results
The results showed that impregnation of HA scaffold with alginate decelerated the degradation rate and reinforced the mechanical strength. TQ loading in alginate/HA had no significant influence on physical and mechanical properties. Real-time RT-PCR showed significant elevation in collagen, osteopontin, and osteocalcin expression at early phase of differentiation. TQ also led to an increase in alkaline phosphatase activity. At long term, TQ administration had no impact on calcium deposition and proliferation rate as well as bone-marker expression.

Conclusion
TQ accelerates the differentiation of the stem cells into the osteoblasts, without changing the physical and mechanical properties of the scaffolds. TQ also showed a synergic influence on differentiation potential of mesenchymal stem cells.
Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice
Authors: Chen Yi , Jiang Zhaohui , Xu Jinzhuan , Zhang Jiyuan , Sun Runbin , Zhou Jia , Lu Yuan , Gong Zipeng , Huang Jing , Shen Xiangchun , Du Qianming , Peng Jianqing 
Published: August 2021

Abstract
Background
The combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD.

Results
DEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathways

Conclusion
DEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.

Graphic abstract
Plasma heat shock protein 90alpha as a biomarker for the diagnosis of liver cancer: in patients with different clinicopathologic characteristics
Authors: Han Yueting , Zhang Youqin , Cui Lin , Li Ze , Feng Honglei , Zhang Ying , Sun Da , Ren Li 
Published: August 2021

Abstract
Purposes
The purposes of this study were to assess the correlation between the plasma level of Hsp90α and the clinicopathological characteristics of patients with liver cancer and compare the diagnostic efficacy of Hsp90α, AFP, CEA, and CA199 in HCC.

Experimental design
A total of 200 individuals, including 140 patients with liver cancer or benign liver diseases and 60 healthy people, were enrolled for quantitative measurement of plasma Hsp90α by ELISA.

Results
The plasma level of Hsp90α was significantly different between patients with liver cancer or benign liver diseases and healthy controls (P < 0.001). The sensitivity, specificity, and AUC (95% CI) of Hsp90α were 93.2%, 85.4%, and 0.931% (0.891–0.972%), respectively, when Hsp90α was applied to differentiate liver cancer patients and healthy controls. Significant positive correlations between the plasma Hsp90α level and clinicopathological characteristics such as the history of basic liver disease (P = 0.038), active stage of hepatitis (P = 0.039), Child-Pugh score (P < 0.001), size of focal liver lesions (P = 0.004), and extrahepatic metastasis (P < 0.001) were observed. AFP + Hsp90α was the best combination strategy for the auxiliary diagnosis of HCC, with a sensitivity of 95.7%, a specificity of 97.5%, and an AUC of 0.990 (0.976–1.000). The level of plasma Hsp90α decreased significantly (P < 0.001) after resection of tumor tissue.

Conclusions
This study demonstrated that plasma Hsp90α levels are useful as a diagnostic biomarker in liver cancer and may predict the responses of patients with liver cancer to surgery. Some clinicopathological characteristics could affect the plasma Hsp90α levels.
Participation of women in the health workforce in the fragile and conflict-affected countries: a scoping review
Authors: Ayaz Basnama , Martimianakis Maria Athina , Muntaner Carles , Nelson Sioban 
Published: August 2021

Abstract
Introduction and background
The full participation of women as healthcare providers is recognized globally as critical to favorable outcomes at all levels, including the healthcare system, to achieving universal health coverage and sustainable development goals (SDGs) by 2030. However, systemic challenges, gender biases, and inequities exist for women in the global healthcare workforce. Fragile and conflict-affected states/countries (FCASs) experience additional pressures that require specific attention to overcome challenges and disparities for sustainable development. FCASs account for 42% of global deaths due to communicable, maternal, perinatal, and nutritional conditions, requiring an appropriate health workforce. Consequently, there is a need to understand the impact of gender on workforce participation, particularly women in FCASs.

Methods
This scoping review examined the extent and nature of existing literature, as well as identified factors affecting women's participation in the health workforce in FCASs. Following Arksey and O'Malley's scoping review methodology framework, a systematic search was conducted of published literature in five health sciences databases and grey literature. Two reviewers independently screened the title and abstract, followed by a full-text review for shortlisted sources against set criteria.

Results
Of 4284, 34 sources were reviewed for full text, including 18 primary studies, five review papers, and 11 grey literature sources. In most FCASs, women predominate in the health workforce, concentrated in nursing and midwifery professions; medicine, and the decision-making and leadership positions, however, are occupied by men. The review identified several constraints for women, related to professional hierarchies, gendered socio-cultural norms, and security conditions. Several sources highlight the post-conflict period as a window of opportunity to break down gender biases and stereotypes, while others highlight drawbacks, including influences by consultants, donors, and non-governmental organizations. Consultants and donors focus narrowly on programs and interventions solely serving women's reproductive health rather than taking a comprehensive approach to gender mainstreaming in planning human resources during the healthcare system’s restructuring.

Conclusion
The review identified multiple challenges and constraints facing efforts to create gender equity in the health workforce of FCASs. However, without equal participation of women in the health workforce, it will be difficult for FCASs to make progress towards achieving the SDG on gender equality.