bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of Graves’ hyperthyroidism with very long-term methimazole treatment: a clinical trial
Authors: Azizi Fereidoun , Abdi Hengameh , Amouzegar Atieh 
Published: January 2021

Abstract
Background
Long-term antithyroid drug therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years.

Methods
Fifty nine patients with Graves’ disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years.

Results
Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study.

Conclusions
Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research.

Trial registration
IRCT201009224794N1, 2010-10-25. Retrospectively registered.
https://www.irct.ir/trial/5143.
The effect of educational program based on theory of planned behavior on promoting retinopathy preventive behaviors in patients with type 2 diabetes: RCT
Authors: Hosseini Seyed Shahriar , Shamsi Mohsen , Khorsandi Mahboobeh , Moradzadeh Rahmatollah 
Published: January 2021

Abstract
Background
Diabetic retinopathy is the most common microvascular complication of diabetes and it is a leading cause of visual impairment and blindness among patients with diabetes. This study aimed to investigate the effect of educational program based on Theory of Planned Behavior (TPB) on promoting retinopathy preventive behaviors in patients with type 2 diabetes.

Methods
The present study is an educational randomized controlled trial research that was conducted on 94 patients with type 2 diabetes who had gone to diabetes clinic. The samples were randomly assigned to the intervention (N = 47) and control groups (N = 47). Data collection instrument was a researcher-made questionnaire based on TPB and FBS and HbA1C tests. Then, educational program was performed for the intervention group through four educational sessions. After 3 months, data collection was repeated for the two groups and FBS, HbA1C testes were done again and data were analyzed.

Results
The performance of the intervention group on preventive behaviors of retinopathy increased from 2.48 ± 1.42 to 4.48 45 1.45 after the education (p < 0.001). The mean of FBS and HbA1c in the intervention group also decreased after the intervention (P < 0.05).

Conclusion
Applying the TPB model proved is very effective in developing an educational program for patients with diabetes, to control their blood sugar and enhance preventive behaviors of retinopathy. Besides such programs, follow-up education for controlling and monitoring are highly recommended. This theory serves as a helpful theoretical framework for health-related behaviors and can be an appropriate pattern to plan for educational interventions.

Trial registration
This trial has been registered at Iranian Registry of Clinical Trials, IRCT20180819040834N1. Prospectively registered 8 Apr 2019, https://en.irct.ir/trial/38401
Fermentation of Panax notoginseng root extract polysaccharides attenuates oxidative stress and promotes type I procollagen synthesis in human dermal fibroblast cells
Authors: You Shiquan , Shi Xiuqin , Yu Dan , Zhao Dan , An Quan , Wang Dongdong , Zhang Jiachan , Li Meng , Wang Changtao 
Published: January 2021

Abstract
Background
Panax notoginseng is one of the most valuable traditional Chinese medicines. Polysaccharides in P. notoginseng has been shown to significantly reduce the incidence of human diseases. However the application of fermentation technology in Panax notoginseng is not common, and the mechanism of action of P. notoginseng polysaccharides produced by fermentation is still unclear. The specific biological mechanisms of fermented P. notoginseng polysaccharides (FPNP) suppresses H2O2-induced apoptosis in human dermal fibroblast (HDF) and the underlying mechanism are not well understood.

Methods
In this study, the effects of water extracted and fermentation on concentration of polysaccharides in P. notoginseng extracts were analyzed. After the H2O2-induced HDF model of oxidative damage was established, and then discussed by the expression of cell markers, including ROS, MDA, SOD, CAT, GSH-Px and MMP-1, COL-I, ELN, which were detected by related ELISA kits. The expression of TGF-β/Smad pathway markers were tested by qRT-PCR to determine whether FPNP exerted antioxidant activity through TGF-β signaling in HDF cells.

Results
The polysaccharide content of Panax notoginseng increased after Saccharomyces cerevisiae CGMCC 17452 fermentation. In the FPNP treatment group, ROS and MDA contents were decreased, reversed the down-regulation of the antioxidant activity and expression of antioxidant enzyme (CAT, GSH-Px and SOD) induced by H2O2. Furthermore, the up-regulation in expression of TGF-β, Smad2/3 and the down-regulation in the expression of Smad7 in FPNP treated groups revealed that FPNP can inhibit H2O2-induced collagen and elastin injury by activating TGF-β/Smad signaling pathway.

Conclusion
It was shown that FPNP could inhibit the damage of collagen and elastin induced by H2O2 by activating the TGF-β/Smad signaling pathway, thereby protecting against the oxidative damage induced by hydrogen peroxide. FPNP may be an effective attenuating healing agent that protects the skin from oxidative stress and wrinkles.
Anatomy Education Environment Measurement Inventory (AEEMI): a cross-validation study in Malaysian medical schools
Authors: Hadie Siti Nurma Hanim , Yusoff Muhamad Saiful Bahri , Arifin Wan Nor , Kasim Fazlina , Ismail Zul Izhar Mohd , Asari Mohd Anizam , Abdul Manan @ Sulong Husnaida , Hassan Asma’ , Muda Tg Fatimah Murniwati Tg , Bakar Yasrul Izad Abu , Zamin Rasheeda Mohd , Ramli Elvy Suhana Mohd , Hod Rafidah , Talip Saiful Bahri , Noor Ku Mastura Ku Mohd , Merican Yusoff Sharizal Yusoff Azmi , Azmi Muhammad Fairuz , Latiff Atikah Abdul , Rushaidhi Madihah 
Published: January 2021

Abstract
Background
The Anatomy Education Environment Measurement Inventory (AEEMI) evaluates the perception of medical students of educational climates with regard to teaching and learning anatomy. The study aimed to cross-validate the AEEMI, which was previously studied in a public medical school, and proposed a valid universal model of AEEMI across public and private medical schools in Malaysia.

Methods
The initial 11-factor and 132-item AEEMI was distributed to 1930 pre-clinical and clinical year medical students from 11 medical schools in Malaysia. The study examined the construct validity of the AEEMI using exploratory and confirmatory factor analyses.

Results
The best-fit model of AEEMI was achieved using 5 factors and 26 items (χ 2 = 3300.71 (df = 1680), P < 0.001, χ 2/df = 1.965, Root Mean Square of Error Approximation (RMSEA) = 0.018, Goodness-of-fit Index (GFI) = 0.929, Comparative Fit Index (CFI) = 0.962, Normed Fit Index (NFI) = 0.927, Tucker–Lewis Index (TLI) = 0.956) with Cronbach’s alpha values ranging from 0.621 to 0.927. Findings of the cross-validation across institutions and phases of medical training indicated that the AEEMI measures nearly the same constructs as the previously validated version with several modifications to the item placement within each factor.

Conclusions
These results confirmed that variability exists within factors of the anatomy education environment among institutions. Hence, with modifications to the internal structure, the proposed model of the AEEMI can be considered universally applicable in the Malaysian context and thus can be used as one of the tools for auditing and benchmarking the anatomy curriculum.
Determinants of successful guideline implementation: a national cross-sectional survey
Authors: Jin Ying-hui , Tan Li-Ming , Khan Khalid S. , Deng Tong , Huang Chao , Han Fei , Zhang Jing , Huang Qiao , Huang Di , Wang Dan-qi , Wang Yu , Zeng Xian-tao , Wang Qiang , Wang Xing-huan 
Published: January 2021

Abstract
Background
CPGs are not uniformly successful in improving care and several instances of implementation failure have been reported. Performing a comprehensive assessment of the barriers and enablers is key to developing an informed implementation strategy. Our objective was to investigate determinants of guideline implementation and explore associations of self-reported adherence to guidelines with characteristics of participants in China.

Methods
This is a cross-sectional survey, using multi-stage stratified typical sampling based on China's economic regional divisions (the East, the Middle, the West and the Northeast). 2–5 provinces were selected from each region. 2–3 cities were selected in each province, and secondary and tertiary hospitals from each city were included. We developed a questionnaire underpinned by recommended methods for the design and conduct of self-administered surveys and based on conceptual framework of guideline use, in-depth related literature analysis, guideline development manuals, related behavior change theory. Finally, multivariate analyses were performed using logistic regression to produce adjusted odds ratios (OR) and 95% confidence intervals (95% CI).

Results
The questionnaire consisted of four sections: knowledge of methodology for developing guidelines; barriers to accessing guideline; barriers to guideline implementation; and methods for improving guideline implementation. There were 1732 participants (87.3% response rate) from 51 hospitals. Of these, 77.2% reported to have used guidelines frequently or very frequently. The key barriers to guideline use were lack of education or training (46.2%), and overly simplistic wording or overly broad scope of recommendations (43.8%). Level of adherence to guidelines was associated with geographical regions (the northeast P < 0.001; the west P = 0.02; the middle P < 0.001 compared with the east), hospital grades (P = 0.028), length of practitioners’ practice (P = 0.006), education background (Ph.D., P = 0.027; Master, P = 0.002), evidence-based medicine skills acquired in work unit (P = 0.012), and medical specialty of practitioner (General Practice, P = 0.006; Surgery, P = 0.043).

Conclusion
Despite general acknowledgement of the importance of guidelines, the use of guidelines was not as frequent as might have been expected. To optimize the likelihood of adherence to guidelines, guideline implementation should follow an actively developed dissemination plan incorporating features associated with adherence in our study.
Highly selective synthesis of d-amino acids via stereoinversion of corresponding counterpart by an in vivo cascade cell factory
Authors: Zhang Dan-Ping , Jing Xiao-Ran , Wu Lun-Jie , Fan An-Wen , Nie Yao , Xu Yan 
Published: January 2021

Abstract
Background
d-Amino acids are increasingly used as building blocks to produce pharmaceuticals and fine chemicals. However, establishing a universal biocatalyst for the general synthesis of d-amino acids from cheap and readily available precursors with few by-products is challenging. In this study, we developed an efficient in vivo biocatalysis system for the synthesis of d-amino acids from l-amino acids by the co-expression of membrane-associated l-amino acid deaminase obtained from Proteus mirabilis (LAAD), meso-diaminopimelate dehydrogenases obtained from Symbiobacterium thermophilum (DAPDH), and formate dehydrogenase obtained from Burkholderia stabilis (FDH), in recombinant Escherichia coli.

Results
To generate the in vivo cascade system, three strategies were evaluated to regulate enzyme expression levels, including single-plasmid co-expression, double-plasmid co-expression, and double-plasmid MBP-fused co-expression. The double-plasmid MBP-fused co-expression strain Escherichia coli pET-21b-MBP-laad/pET-28a-dapdh-fdh, exhibiting high catalytic efficiency, was selected. Under optimal conditions, 75 mg/mL of E. coli pET-21b-MBP-laad/pET-28a-dapdh-fdh whole-cell biocatalyst asymmetrically catalyzed the stereoinversion of 150 mM l-Phe to d-Phe, with quantitative yields of over 99% ee in 24 h, by the addition of 15 mM NADP+ and 300 mM ammonium formate. In addition, the whole-cell biocatalyst was used to successfully stereoinvert a variety of aromatic and aliphatic l-amino acids to their corresponding d-amino acids.

Conclusions
The newly constructed in vivo cascade biocatalysis system was effective for the highly selective synthesis of d-amino acids via stereoinversion.
Mapping experiences and perspectives of equity in international health collaborations: a scoping review
Authors: Faure Marlyn C. , Munung Nchangwi S. , Ntusi Ntobeko A. B. , Pratt Bridget , de Vries Jantina 
Published: January 2021

AbstractBackgroundWhilst global health research often involves international collaborations, achieving or promoting equity within collaborations remains a key challenge, despite established conceptual approaches and the development of frameworks and guidelines to promote equity. There have also been several empirical studies documenting researchers’ experiences of inequity and views on what is required to advance equity in global health collaborations. While these empirical studies provide critical insights, there has been no attempt to systematically synthetize what constitutes equity and how it can be achieved. To address this gap, we conducted a scoping review of qualitative studies, opinion and editorial pieces about what equity is and how it can be promoted in international collaborations.MethodsWe conducted a scoping review to explore domains of equity in international health collaborations. This review included qualitative studies and opinion pieces or editorial pieces on equity in international health collaborations. We mapped the data and identified common themes using a thematic analysis approach.ResultsThis initial search retrieved a total of 7611 papers after removing duplicates. A total of 11 papers were included in this review, 10 empirical studies and 1 editorial piece. We conducted our search between October – November 2019. We identified 10 key domains which are important for promoting equity in international collaborations: funding; capacity building; authorship; sample ownership and export; trust; research agreement; acknowledging inequality; recognition and communication.DiscussionOur findings suggest that for international collaborations to be considered more equitable, it must at least consider the 10 domains we highlighted. The 10 domains map onto five key aspects of social justice theory, namely avoiding unequal power relations like subordination, group recognition and affirmation, promoting the well-being of all, inclusion in decision-making and ensuring self-development.
Propofol suppresses microglial phagocytosis through the downregulation of MFG-E8
Authors: Cai Xiaoying , Li Ying , Zheng Xiaoyang , Hu Rong , Li Yingyuan , Xiao Liangcan , Wang Zhongxing 
Published: January 2021

Abstract
Background
Microglia are highly motile phagocytic cells in the healthy brain with surveillance and clearance functions. Although microglia have been shown to engulf cellular debris following brain insult, less is known about their phagocytic function in the absence of injury. Propofol can inhibit microglial activity, including phagocytosis. Milk fat globule epidermal growth factor 8 (MFG-E8), as a regulator of microglia, plays an essential role in the phagocytic process. However, whether MFG-E8 affects the alteration of phagocytosis by propofol remains unknown.

Methods
Microglial BV2 cells were treated with propofol, with or without MFG-E8. Phagocytosis of latex beads was evaluated by flow cytometry and immunofluorescence. MFG-E8, p-AMPK, AMPK, p-Src, and Src levels were assessed by western blot analysis. Compound C (AMPK inhibitor) and dasatinib (Src inhibitor) were applied to determine the roles of AMPK and Src in microglial phagocytosis under propofol treatment.

Results
The phagocytic ability of microglia was significantly decreased after propofol treatment for 4 h (P < 0.05). MFG-E8 production was inhibited by propofol in a concentration- and time-dependent manner (P < 0.05). Preadministration of MFG-E8 dose-dependently (from 10 to 100 ng/ml) reversed the suppression of phagocytosis by propofol (P < 0.05). Furthermore, the decline in p-AMPK and p-Src levels induced by propofol intervention was reversed by MFG-E8 activation (P < 0.05). Administration of compound C (AMPK inhibitor) and dasatinib (Src inhibitor) to microglia blocked the trend of enhanced phagocytosis induced by MFG-E8 (P < 0.05).

Conclusions
These findings reveal the intermediate role of MFG-E8 between propofol and microglial phagocytic activity. Moreover, MFG-E8 may reverse the suppression of phagocytosis induced by propofol through the regulation of the AMPK and Src signaling pathways.
Regional cooperation is essential to combatting health emergencies in the Global South
Authors: Amaya Ana B. , De Lombaerde Philippe 
Published: January 2021

AbstractSince COVID-19 was first discovered, it exploded into a pandemic resulting in devastating effects on human lives and a global recession. While there have been discussions that COVID-19 will accelerate the ‘end of globalization and multilateralism’, we have already seen the high costs of non-cooperation in responding to the virus resulting in sub-optimal use of resources, rapid spread of the virus between countries, and, ultimately, significant loss of life. In spite of their favorable demographic structures and relatively young populations, countries in the Global South are still harshly affected in both epidemiological and economic terms. Nations must find innovative ways to address health concerns and regional bodies are possible mechanisms for facilitating international cooperation on health. We delineate how regional organizations can support how countries address health threats namely by serving as a bridge between the global and national policy levels; strengthening disease surveillance; mobilizing supply chains and facilitating trade; supporting the production and procurement of medicines and supplies; and coordinating policies and work with other actors. We finalize by arguing that mechanisms for regional cooperation must be strengthened themselves in order to effectively contribute to positive health outcomes within member states.
Expression of IL4Rα and IL13Rα1 are associated with poor prognosis of soft-tissue sarcoma of the extremities, superficial trunk, and retroperitoneum
Authors: Kim Kyoung Min , Hussein Usama Khamis , Park See-Hyoung , Moon Young Jae , Zhang Zhongkai , Ahmed Asmaa Gamal , Ahn Ae-Ri , Park Ho Sung , Kim Jung Ryul , Jang Kyu Yun 
Published: January 2021

Abstract
Background
IL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited.

Methods
This study investigated the immunohistochemical expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. Immunohistochemical staining for IL4Rα and IL13Rα1 were scored according to a combination of staining intensity and staining area in tissue microarray samples. Positivity for the immunohistochemical expression of IL4Rα and IL13Rα1 were determined using receiver operating curve analysis. Statistical analysis was performed using regression analysis and a chi-square test.

Results
In human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p < 0.001) of soft-tissue sarcoma patients. Moreover, the co-expression pattern of nuclear IL4Rα and IL13Rα1 was an independent indicator of shorter survival of soft-tissue sarcoma patients (overall survival; overall p < 0.001, relapse-free survival; overall p < 0.001).

Conclusions
This study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.
Fibrinogen performs better than D-dimer for the diagnosis of periprosthetic joint infection: a meta-analysis of diagnostic trials
Authors: Pan Liping , Wu Hao , Liu Heng , Yang Xin , Meng Zhichao , Cao Yongping 
Published: January 2021

Abstract
Purpose
D-dimer and fibrinogen, both belonging to coagulation parameters, are controversial for the diagnosis of periprosthetic joint infection (PJI). This meta-analysis was conducted to compare their diagnostic accuracies for PJI by synthesizing currently available evidence.

Methods
Cochrane Library, MEDLINE, Web of Science, and Embase up to March 1, 2020, and other relevant articles were searched. Five hundred and eighty-one articles were identified after initial research, and 11 studies were included finally. No threshold effects were found between studies. The pooled sensitivity, specificity, and positive and negative likelihood ratio were reported to evaluate the diagnostic performance with heterogeneity analysis. Z test statistics was used to analyze the difference of diagnostic performance between D-dimer and fibrinogen.

Results
The pooled sensitivity, specificity, and positive and negative likelihood ratio of D-dimer for PJI were 0.79 (95% [CI], 0.72–0.85), 0.77 (0.67–0.84), 3.38 (2.21–5.18), and 0.27 (0.18–0.41), respectively. As for fibrinogen, the pooled sensitivity, specificity, and positive and negative likelihood ratio for PJI were 0.75 (0.68–0.80), 0.85 (0.82–0.88), 5.12 (4.22–6.22), and 0.30 (0.23–0.37), respectively. Great heterogeneity was found in studies for D-dimer, and univariate meta-regression analysis revealed that number of involved joints, disease spectrum, comorbidities influencing D-dimer, and sample sources were the source of heterogeneity. Z test found that the pooled specificity of fibrinogen was significantly higher than D-dimer (0.85 ± 0.01 versus 0.77 ± 0.04, p = 0.03). The pooled positive likelihood ratio of fibrinogen was significantly higher than D-dimer (5.12 ± 0.51 versus 3.38 ± 0.74, p = 0.03).

Conclusion
Based on currently available evidence, the meta-analysis suggests that fibrinogen performs better than D-dimer as a rule-in diagnostic tool for its higher specificity. However, more prospective trials with larger size are still needed to provide further confirmation.

Trial registration
This meta-analysis was prospectively registered on PROSPERO (International prospective register of systematic reviews), and the registering number was CRD42020177176.