bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the Crisis in Harm Reduction Funding in Central and Eastern Europe
Authors: Miovský Michal , Miklíková Silvia , Mravčík Viktor , Grund Jean-Paul , Černíková Tereza 
Published: August 2020

Abstract
BACKGROUND: The harm reduction (HR) approach to injecting drug use was rapidly adopted in Central Europe following the fall of the Iron Curtain. The associated social and economic transformationhad significant consequences for drug policies in the region. A large number of the emerging services have been dependent on funding from a wide range of national and/or local funding programmes, which continue to be unstable,and closelyassociated with political decisions and insufficient institution building. A sharp distinction is made between health and social services, often without regard to client input.The main objectiveof the paper is to identify the causes of the funding problems currently faced by HR services in the context of their history of institution buildingwhich represents a major threatto the future of HR services in the region. METHODS: Qualitative content analysis of documents was conducted in the development of two case studies of the Czech and Slovak Republics. The body of documentation under study comprised policy documents, including National Drug Strategies, Action Plans, ministerial documents, and official budgets and financial schedules, as well as documents from the grey literature and expert opinions.RESULTS: The insufficient investments in finalising the process of the institution building of HR services has resulted in a direct threat to their sustainability. An unbalanced inclination to the institutionalisation of HR within the domain of social services has led to a misperception of their integrity, as well as to their funding and long-term sustainability being endangered. In addition, this tendency has had a negative impact on the process of the institutionalisation of HR within the system of healthcare. CONCLUSION:The case study revealed a lack of systemic grounding of HR services as interdisciplinary health-social services. The aftermath of the financial crisis in 2008 fully revealed the limitations of the funding system established ad hoc in the 1990s,which remains present until today, togetherwith all its weak points. The entire situation is responsible for the dangerous erosion of the interpretation of the concept of harm reduction, which is supported by various stereotypes and false, or ideological, interpretations of the concept.
Rapid emergence of clonal interference during malaria parasite cultivation
Authors: Jett Catherine , Dia Aliou , cheeseman ian H. 
Published: August 2020

Abstract
Laboratory cultivation of the malaria parasite Plasmodium falciparum has underpinned nearly all advances in malariology in the past 30 years. When freshly isolated clinical isolates are adapted to in vitro culture mutations rapidly fix increasing the parasite growth rate and stability. While the dynamics of culture adaptation are increasingly well characterized, we know little about the extent of genomic variation that arises and spreads during long term culture. To address this we cloned the 3D7 reference strain and maintained a culture for ~84 asexual cycles (167 days). Growth rate of the culture population increased 1.14-fold over this timeframe. We used single cell genome sequencing of parasites at cycles 21 and 84 to measure the accumulation of diversity in vitro . This parasite population showed strong signals of adaptation across this time frame. By cycle 84 two dominant clades had arisen and were segregating with the dynamics of clonal interference. This highlights the continual process of adaptation in malaria parasites, even in parasites which have been extensively adapted to long term culture.
Accuracy of Intraoperative Estimation of Femoral Stem Anteversion in Cementless Total Hip Arthroplasty by Using a Digital Protractor and a Spirit Level
Authors: Pongkunakorn Anuwat , Phetpangnga Nawakun , Kananai Narawit 
Published: August 2020

Abstract
Introduction: The femoral component anteversion during surgery is traditionally assessed by a visual assessment of the surgeon and has proven to be imprecise. We sought to determine the accuracy of a digital protractor and a spirit level to measure the stem anteversion during cementless THA.Methods: A prospective study was conducted among 107 patients (114 hips) who underwent primary cementless THA via posterolateral approach. A pipe with a spirit level was attached to the tibial tubercle and intermalleolar midpoint. While the leg was held perpendicularly to the floor, stem anteversion was estimated by 3 methods: method A by visual assessment; method B by a digital protractor alone; and method C by a digital protractor combined with a spirit level. The angles were compared with the true anteversion measured by postoperative CT scan.Results: The average anteversion by method C (22.8° ± 6.9°, range -2° to 40°) was significantly lower than method A (24.6° ± 5.2°, range 0° to 30°) (p=0.033), but not different from the true anteversion (22.1° ± 8.2°, range -5.4° to 43.1°) (p=0.445). There were no significant differences between method B (23.2° ± 8.2°, range -4° to 45°) and method A, C or the true anteversion. The mean deviation of the intraoperative estimation from the true anteversion was 0.8° ± 3.7° (range -7.1° to 8.0°) by method C; 1.2° ± 5.1° (range -8.8° to 14.3°) by method B; and 2.5° ± 7.4° (range -19.0° to 16.0°) by method A. Estimation error within 5° was found in 107 hips (93.9%) with method C; 86 hips (75.4%) with method B; and 59 hips (51.8%) with method A.Conclusion: Accurate estimation of stem anteversion during cementless THA can be determined intraoperatively by the use of a digital protractor and a spirit level. Trial registration: Thai Clinical Trials Registry (TCTR 20180326003). Registered on 20 March 2018. Retrospectively registered. http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=3375
Tidal surface states as ﬁngerprints of non-Hermitian nodal knot metals
Authors: Lee Ching Hua , Li Guangjie , Liu Yuhan , Tai Tommy , Thomale Ronny , Zhang Xiao 
Published: August 2020

Abstract
The paradigm of metals has undergone a revision and diversification from the viewpoint of topology. Non-Hermitian nodal knot metals (NKMs) constitute a class of matter without Hermitian analog, where the intricate structure of complex-valued energy bands gives rise to knotted lines of exceptional points and new topological surface state phenomena. We introduce a formalism that connects the algebraic, geometric, and topological aspects of these surface states with their underlying parent knots, and complement our results by an optimized constructive ansatz that provides tight-binding models for non-Hermitian NKMs of arbitrary knot complexity and minimal hybridization range. In particular, we identify the surface state boundaries as ``tidal' intersections of the complex band structure in a marine landscape analogy. We further find these tidal surface states to be intimately connected to the band vorticity and the layer structure of their dual Seifert surface, and as such provide a fingerprint for non-Hermitian NKMs.
Cell type-specific predictive models for prioritizing genes and gene sets associated with autism spectrum disorder
Authors: Guan Jinting , Wang Yang , Lin Yiping , Yin Qingyang , Zhuang Yibo , Ji Guoli 
Published: August 2020

Abstract
Background Autism spectrum disorder (ASD) is characterized by substantial phenotypic and genetic heterogeneity. Although bulk transcriptomic analyses revealed convergence of disease pathology on common pathways, the brain cell type-specific molecular pathology of ASD is still needed to study. Different gene functions may be dysregulated and causal genes may be distinct among different brain cells in ASD. Gene expression profiling-based machine learning studies can be conducted for the diagnosis of ASD, prioritizing high-confidence gene candidates and promoting the design of effective interventions.Methods To characterize the cell type heterogeneity of ASD and to take advantage of the potential of gene expression signature as diagnostic biomarkers for ASD, we construct multiple kinds of classification models for ASD based on the recently available human brain nucleus gene expression data of ASD and controls. Firstly, we construct cell type-specific predictive models based on individual genes to screen cell type-specific genes associated with ASD. Then from the view of gene set, we construct cell type-specific gene set-based predictive models to screen cell type-specific gene sets associated with ASD. These two kinds of predictive models can be applied to predict the diagnosis of a given nucleus with known cell type. Lastly, we further construct a multi-label predictive model for predicting the cell type and diagnosis of a given nucleus at the same time.Results It is found that the functions of genes with predictive power for ASD are not consistent and the top important genes are distinct among different cells, demonstrating the cell type heterogeneity of ASD. Our findings suggest that layer 2/3 and layer 4 excitatory neurons, layer 5/6 cortico-cortical projection neurons, parvalbumin interneurons, and protoplasmic astrocytes are preferentially affected in ASD. Gene BCYRN1 and CCK are prioritized in excitatory neurons, and HSPA1A is of note in protoplasmic astrocytes.Limitations Our study utilized methods of machine learning to identify biomarkers of ASD, while it is more convincing if subsequent experiments could be conducted to validate the results.Conclusions The results show that it may be feasible to use single cell/nucleus gene expression for ASD detection and the constructed predictive models can promote the diagnosis of ASD. Our analytical pipeline prioritizes ASD-associated cell type-specific genes and gene sets, which may be used as potential biomarkers of ASD.
Enhancement of Monascus Azaphilone Pigments Production by Activating the cAMP Signalling Pathway in Monascus Purpureus HJ11
Authors: Liu Jiawei , Du Yun , Ma Hongmin , Pei Xiaolin , Li Mu 
Published: August 2020

Abstract
Background: Monascus azaphilone pigments (MonAzPs), which were produced by Monascus species, have been used as important food colorant and food supplements for more than one billion people during their daily life. Moreover, MonAzPs recently have received more attention because of their diverse physiological activities. However, the high microbial production of MonAzPs is still not always guaranteed. Herein, the aim of this study was to develop an efficient biotechnological process for MonAzPs production.Results: In this study, exogenous cyclic adenosine monophosphate (cAMP) treatment not only induced MonAzPs production, but also stimulated the expression of a cAMP phosphodiesterase gene, named as mrPDE, in M. purpureus HJ11. Subsequently, MrPDE was identified as a cAMP phosphodiesterase by in vitro enzymatic reaction with purified enzyme. Further, a gene knockout mutant of mrPDE was constructed to verify the activation of cAMP signalling pathway. Deletion of mrPDE in M. purpureus HJ11 improved cAMP concentration by 378 % and enhanced PKA kinase activity 1.5-fold, indicating that activation of cAMP signalling pathway was achieved. The ΔmrPDE strain produced MonAzPs at 8563 U/g, with a 2.3-fold increase compared with the WT strain. Moreover, the NAPDH/NADP+ ratio of the ΔmrPDE strain was obviously higher than that of the wild type strain, which led to a higher proportion of yellow MonAzPs. With fed-batch fermentation of the ΔmrPDE strain, the production and yield of MonAzPs achieved 332.1 U/mL and 8739 U/g.Conclusions: A engineered M. purpureus strain for high MonAzPs production was successfully developed by activating the cAMP signalling pathway. This study not only describes a novel strategy for development of MonAzPs-producing strain, but also provides a roadmap for engineering efforts towards the production of secondary metabolism in other filamentous fungi.
Treatment of Osteosarcoma from the Spine: A Population-Based Database Study
Authors: Tang Chao , Wang Ruiliang , Xu Hengyuan , Zhang Hailong 
Published: August 2020

Abstract
PurposeThe treatment of osteosarcoma of the spine remains controversial. Our aim is to explore the treatment of patients with spinal osteosarcoma. MethodsWe analyzed the date collected 727 spinal osteosarcoma patients from the Surveillance Epidemiology and End Results (SEER) databases between 1973 and 2015. X-tile software was performed to find the optimal cut-off values of age and economic income. Univariate and Multivariate Cox analyses were used to identify the independent prognostic factors. Logistic regression model was conducted to clear the factors associated to surgical compliance; Kaplan-Meier estimator method was adopted to analyze the Overall survival (OS) and Cancer-specific survival (CSS). ResultsAmong 727 eligible spinal osteosarcoma patients, 370 (50.9%) patients received surgical treatment, 357 (49.1%) cases without surgery. There were significant differences in the effects of age at diagnosis, SEER historic stage and tumor grade on surgical treatment (All P < 0.05). Surgery was an independent prognostic factor for OS and CSS of spinal osteosarcoma patients. Spinal osteosarcoma patients undergone surgery group showed favorable survival than the other group.ConclusionsSurgery can provide survival benefits for patients with osteosarcoma of the spine. Spinal osteosarcoma patients with undergone surgery have favorable survival and surgery can become a suitable treatment for patients.
Establishment of a pediatric surgical unit at a university hospital in Eastern Africa
Authors: Hubertus Jochen , Abera Gersam , Haileamlak Abraham , Siebeck Matthias , von Schweinitz Dietrich , Wagner Ferdinand , Eckle Rosa , Wessel Lucas , Ritz Laura Antonia , Berger Michael Fabian , Ardelean Mircia , Becker Kristina , Seifu Alemu 
Published: August 2020

Abstract
Background
Ethiopia is a rapidly developing country in Eastern Africa. 43.2% of the population is younger than 15. In contrast, until a few years ago, pediatric surgery was only available in Addis Ababa. Now, Ethiopia is making great efforts to improve the care of surgical ill children. JimmaChild was established to set up a pediatric surgery in Jimma.
Methods
JimmaChild developed from a scientific collaboration between Jimma University (JU) and Ludwig-Maximilians-University. The project was developed and realized by Ethiopian and German colleagues. A curriculum was written for this purpose. The pediatric surgical training of the fellows was carried out on-site by German pediatric surgeons.
Results
A new pediatric surgery was established at JU with its own operating room, ward, and staff. After two and a half years, two fellows completed their final examinations as pediatric surgeons. Among others, 850 elective surgeries were performed, 82% assisted by the German colleagues. The German colleagues rated the preparation for the trip, the on-site support, and the professional progress of the fellows mostly as good to very good. Reported problems in the program flow were also recognized and solved in part.
Conclusions
Best possible integration of the project into existing structures was achieved by close cooperation of Ethiopian and German colleagues during the project development. Problems were identified and addressed early on by external monitoring. As the project responsibility was mainly with the Ethiopian colleagues, a department was created that now exists independent of external funding and trains its own fellows.
High-dose vitamin C infusion for the treatment of critically ill COVID-19
Authors: Zhang Jing , Rao Xin , Li Yiming , Zhu Yuan , Liu Fang , Guo Guangling , Luo Guoshi , Meng Zhongji , Backer Daniel De , Xiang Hui , Peng Zhi-Yong 
Published: August 2020

Abstract
BackgroundNo specific medication has been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19.MethodsThis randomized, controlled clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 hours for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way. The primary outcome was invasive mechanical ventilation-free days in 28 days(IMVFD28). Secondary outcomes were 28-day mortality, organ failure, and inflammation progression.ResultsFifty-four critical COVID-19 patients were ultimately recruited. There was no difference in IMVFD28 between two groups. During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P = 0.01). Patients with SOFA scores ≥ 3 in the HDIVC group exhibited a significant reduction in 28-day mortality (P = 0.05) in univariate survival analysis. IL-6 in the VC group was lower than that in the placebo group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P = 0.04) on day 7.ConclusionThe addition of HDIVC may provide a protective clinical effect without any adverse events in critically ill patients with COVID-19.Clinicaltrial.gov identifer: NCT04264533
The Cingulate Structures in Autism Spectrum Disorder: Exploring Its Implication on Social Awareness and the Role of CNTNAP2
Authors: Chien Yi-Ling , Chen Yu-Chieh , Gau Susan Shur-Fen 
Published: August 2020

Abstract
Backgrounds Although evidence suggests that the activity of the anterior cingulate cortex involves social cognition, there are inconsistent results regarding the aberrant cingulate gray matter (GM) and scanty evidence about altered cortical thickness and white matter (WM) of cingulate in individuals with autism spectrum disorder (ASD). Evidence supports the association between the autism risk gene CNTNAP2 variants and altered brain connectivity. This study investigated the cingulate substructure and its association with social awareness deficits and the CNTNAP2 variants in individuals with ASD. Methods We assessed 122 individuals with ASD and 118 typically-developing controls (TDC) with MRI and clinical evaluation. The GM, WM volumes and cortical thickness of the cingulate gyrus were compared between ASD and TDC based on fine parcellation. Five SNPs of the CNTNAP2 linking to ASD and brain structural abnormality were genotyped. Results ASD individuals showed thinner cortical thickness in bilateral cingulate subregions than TDC but no significant group differences in GM and WM volumes. The WM volume of the right anterior cingulate gyrus was correlated with social awareness deficits in ASD. Two CNTNAP2 variants demonstrated the main effects on the WM volumes of the right middle cingulate gyrus and the cortical thickness of the right posterior ventral cingulate gyrus. Besides, the CNTNAP2 variants interacted with ASD status and age on the cortical thickness of the left anterior middle cingulate cortex.Limitations The CNTNAP2 variants selected in this study were based on the current literature that repeatedly revealed genetic associations with ASD and brain structures. Future studies may consider fine mapping or sequencing of this gene. Besides, we measured social awareness deficits by caregiver-report questionnaire. Although the observation from caregivers may reflect social function in daily life, a social cognition task may better provide a standardized measurement.Conclusions Our findings suggest that aberrant cingulate structure in ASD may be associated with the severity of autistic symptoms and genetic variants of the CNTNAP2. These novel findings need validation. Trial registration: ClinicalTrials.gov number, NCT01582256
Structural Equation Modeling for Identification of Patient Safety Antecedents in Primary Care
Authors: Kosiek Katarzyna , Staniec Iwona , Godycki-Cwirko Maciej , Depta Adam , Kowalczyk Anna 
Published: August 2020

Abstract
Background: To create an integrative model of patient safety, concerning antecedents based on the perception of patient safety improvement strategies expressed by primary care professionals: facilities available in the practice, communication and collaboration, education on patient safety and generic conditions for patient safety. Methods: We attended several conferences and seminars in Poland where we presented these strategies. In this way, we gained contacts with doctors potentially interested in patient safety. We ensured ourselves contact persons who could respond to our questionnaire. Those persons assured us that they would send the names of prospective respondents. In this research we were used questionnaire form research Gaal S, Verstappen W, Wensing M (1). The results were analyzed with SPSS 20 and AMOS. A hypothetical model of direct and indirect effects on patient safety in a primary care environment was created and analyzed using structural equation modeling (SEM). Results: Improved implementation of strategies was directly and indirectly associated with better patient safety. SEM proved to be an effective tool to analyse safety in primary care. The facilities in the practice appear to have no significant influence on patient safety management in the case of female respondents, those age lower than mean, current professional discipline is not GP and respondents not work in counselling centres.Conclusions: The following should be improved to ensure patient safety: Generic conditions for patient safety, facilities in the practice, communication and collaboration, and education on patient safety.