bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progenitor Cells Derived From Injured Cartilage Surface Respond to Damage Associated Molecular Patterns
Authors: Ding Lei , Zhou Cheng , Zheng Hongjun , Wang Quanming , Song Haiyan , Buckwalter Joseph A. , Martin James A. 
Published: December 2020

Abstract
Objective: To elucidate how chondrogenic progenitor cells (CPCs) originated from mechanically injured cartilage surface respond to proinflammatory endogenous damage-associated-molecular-patterns (DAMPs). Design: Passage 1 bovine CPCs and non-CPCs isolated from injured articular cartilage either by blunt impaction or by scratches were treated with mitochondrial DAMPs (MTDs) composed of fMLF and CpG DNA, or HMGB1 (a nuclear DAMP), or IL-1b for 24 hrs. At the end of the experiments, the expression levels of matrix metalloproteinases (MMPs), chemokines, and cytokines that are associated with cartilage degeneration was examined with Western blotting and quantitative PCR. Results: Both HMGB1 and MTDs remarkably up-regulated expression level of pro-MMP-13 protein in CPCs while showed weak effect on non-CPCs. Compared to non-CPCs, CPCs expressed significantly higher baseline mRNA levels of MMP-13, CXCL12, and IL-6. MTDs further increased the expression levels of MMP-13 and IL-6 in CPCs while HMGB1 did not show such effect. When treated with MTDs, CPCs also expressed significantly higher levels of IL-8 mRNA than did non-CPCs. However, compared to non-CPCs, CPCs expressed much lower levels of MMP-3 and active MMP-13 proteins as well as lower mRNA levels of CCL2 and IL-6 in response to IL-1b. Conclusions: CPCs were more sensitive than non-CPCs in response to DAMPs, especially MTDs, to up-regulate expression of MMP-13, IL-6 and -8. When IL-1b was present, CPCs were less responsive than non-CPCs in terms of up-regulating MMP-3, CCL2, and IL-6 expression. The proinflammatory nature of CPCs implied their critical role in the early phase of PTOA development.
Inheritance of Summer Dormancy, Persistence and Productivity Using Half-sib Matting in Tall Fescue&nbsp;
Authors: Pirnajmedin Fatemeh , Majidi Mohammad Mahdi , Taleb Mohammad Hadi , Maibody Sayed Ali Mohammad Mirmohammady 
Published: December 2020

Abstract
Background: The genetic basis and variability of persistence and summer dormancy and their association with forage production traits has been less investigated in tall fescue. Results: High genotypic variation was found for all the measured traits in both parental genotypes and half-sib families. Incomplete summer dormancy was found for most of the evaluated genotypes. Summer dormancy index were negatively correlated with forage production and yield related traits. Half-sib families had higher persistence than parental genotypes, which can be due to the heterosis expression in progenies. Moderate narrow-sense heritability for persistence indicates that both additive and dominant gene action may play a role in the expression of this trait. Yield-related traits and summer dormancy showed moderate to high estimates of narrow sense heritability (0.63-0.73) indicates additive gene action for these traits. This suggest phenotypic recurrent selection can be successful to achieve genetic progress. Conclusion: In conclusion, our results can enhance the knowledge of inheritance of summer dormancy and related traits which would be useful for future genetic studies. Based on the general combining ability and application of multivariate analysis, preferable genotypes for forage use (such as 21M and 1E) and turf application (such as 17M and 4E) were identified for future programs.
Evaluating the Prognostic Performance of a Polygenic Risk Score for Breast Cancer Risk Stratification
Authors: Olsen Maria , Fischer Krista , Bossuyt Patrick M. , Goetghebeur Els 
Published: December 2020

Abstract
Background: Polygenic risk scores (PRS) could potentially improve breast cancer screening recommendations. We analyzed how well a recently developed prevalence-based breast cancer PRS (Läll et al., 2009) performs in expressing women’s future risk of incident breast cancer. Objectives: To evaluate the prognostic performance of models using PRS and age as predictors, vs age alone, for breast cancer incidence in women from the Estonian biobank (EstBB) cohort. Methods: We analyzed data on 30,312 women from the EstBB cohort. They entered the cohort between 2002 and 2011, were between 20-89 years, without history of breast cancer, and with full 5-year follow-up by 2015. We examined PRS and other potential risk factors as possible predictors in Cox regression models for breast cancer incidence. With 10-fold cross validation we estimated 3- and 5-year breast cancer incidence from age alone and PRS plus age, fitting models on 90% of the data. Calibration, discrimination, and reclassification then expressed prognostic performance on the left-out folds. Results: A total of 101 (3.33‰) and 185 (6.1‰) incident breast cancers were observed within 3 and 5 years, respectively. For women in the current Estonian screening age (50-62 years), the ratio of observed vs PRS-age modelled 3-year incidence was 0.86 for women in the 75-85% PRS-group, 1.34 for the 85-95% PRS-group, and 1.41 for the top 5% PRS-group. For 5-year incidence, this was respectively 0.94, 1.15, and 1.08. Yet, the number of breast cancer events were relatively low in each PRS-subgroup. The model’s AUC was 0.720 (95% CI: 0.675-0.765) for 3-year and 0.704 (95% CI: 0.670-0.737) for 5-year, respectively, just 0.022 and 0.023 higher than for the model with age alone. Using a 1% risk prediction threshold, the 3-year NRI for the PRS-age model was 0.09 and 0.05 for 5 years.Conclusion: The model including PRS had modest incremental performance. This suggests that the potential benefit of adding PRS to age for guiding screening likely affects a relatively small proportion of women. A larger, independent study is needed to assess whether and how the PRS can meaningfully contribute to developing more efficient screening strategies.
Isolated Congenital Cleft Mitral Valve Leaflet: A Rare Cause of Refractory Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: Bahrami Mubashir Hamid , Ansari Hamza , Guglin Maya , Ephrem Georges , Revtyak George 
Published: December 2020

Abstract
We report a unique presentation of isolated congenital cleft mitral valve complicating cardiogenic shock from acute myocardial infarction. Isolated cleft mitral valve is an uncommon diagnosis that can have significant clinical implications, especially if not recognized in patients presenting to the catheterization lab with acute myocardial infarction and cardiogenic shock. A review of this rare diagnosis including the options and timing of therapeutic interventions, which can include MitraClip, is important for publication.The case is of a patient who presented with an anterior acute ST elevation myocardial infarction. Despite early coronary revascularization and conventional support, refractory cardiogenic shock ensued requiring mechanical circulatory support escalation to Veno-arterial extracorporeal membrane oxygenation. Subsequently, left ventriculography revealed a massively dilated left atrium and severe mitral regurgitation raising concerns for a mechanical mitral valve complication. The patient was taken to the operating room for possible mitral valve surgery, but a preoperative transesophageal echocardiogram revealed an isolated posterior cleft mitral valve. Since the patient had stabilized on mechanical circulatory support, emergent surgery was deferred. The patient successfully recovered during index hospitalization with mechanical circulatory support and discharged on guideline directed medical therapy. In conclusion, isolated cleft mitral valve is a rare diagnosis that can often be underrecognized without comprehensive 3-dimensional transesophageal echocardiography evaluation. If diagnosed early with significant regurgitation, surgical treatment results in good outcomes and preservation of LV systolic function. Percutaneous correction of a CMVL with MitraClip has been described and may offer an alternative approach for high risk surgical patients.
Effect of Liuzijue Breathing Exercise on Patients With Stable Chronic Obstructive Pulmonary Disease: A Systemic Review and Meta-analysis
Authors: Gao Pincao , Tang Fang , Liu Weiguo , Mo Yu 
Published: December 2020

Abstract
Backgrounds:Chronic obstructive pulmonary disease(COPD) is a common,preventable disease of airflow limitation that accounts for the third lec deaths in the worldwide.Health benefits of Liuzijue breathing exercise on patients with stable COPD has been assessed.This study was designed to perform a systemic review and meta-analysis of the effect of Liuzijue breathing exercise on patients with stable COPD.Methods: Published articles from inception to 2020 were conducted using electronic searches. Data extraction was performed by two independents reviewers.The Cochrane risk of bias assessment tool was used to assess the quality of the included studies.Results:A total of 16 eligible trials with 1039 patients with stable COPD were identified. Compared with control group,the pool meta-analysis of Liuzijue breathing exercise showed a significant improve in FEV1 [MD=-0.16,95%CI (0.09,0.23), P<0.00001], FEV1% [MD=9.71, 95%CI(8.44,10.98), P<0.00001], FEV1/FVC(%) [MD=4.81,95%CI(2.12,7.51),P=0.0005],6MWD [MD=21.89,95%CI（14.67, 29.11）,P<0.00001] , health-related quality of life [SMD=-0.84,95%CI（-1.12,-0.55，P<0.00001] and mMRC [MD= -0.73,95%CI (-0.96,-0.50), P<0.00001]. The observed effect was more pronounced for interventions that were short term and medium-term duration of study. Liuzijue interventions also showed improvement in the secondary outcome measures.Conclusions:In this systematic review and meta-analysis ,Liuzijue breathing exercise can improve lung function,exercise endurance and health-related quality of life of patients with stable COPD.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero PROSPERO registration number:CRD42020209191.
Protocol for a Systematic Review of Policies, Programs or Interventions Designed to Improve Health and Psychosocial Outcomes for Young People Leaving the Out of Home Care System
Authors: Taylor David John Anthony , Shlonsky Aron S. , Albers Bianca , Chakraborty Sangita , Lewis Jane , Mendes Phillip , Macdonald Geraldine , Williams Kevin 
Published: December 2020

Abstract
Background:Relative to their counterparts in the general population, young people who leave, or transition out of, out-of-home (OOHC) arrangements, commonly experience poorer outcomes across a range of indicators, including: higher rates of homelessness, unemployment, reliance on public assistance, physical and mental health problems, and contact with the criminal justice system. The age at which young people transition from OOHC varies between and within some countries, but for most, formal support ceases between the ages of 18 and 21.Programs designed to support transitions are generally available to young people toward the end of their OOHC placement, although some can extend beyond. They often encourage the development of skills required for continued engagement in education, obtaining employment, maintaining housing and general life skills. Little is known about the effectiveness of these programs, or of extended care policies that raise the age at which support remains available to young people after leaving OOHC. This systematic review will seek to identify programs and/or interventions that improve outcomes for youth transitioning from the OOHC system into adult living arrangements.Methods:Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines, this review will identify programs, interventions and policies that seek to improve health and psychosocial outcomes amongst this population that have been tested using robust controlled methods. Primary outcomes of interest are homelessness, health, education, employment, exposure to violence and risky behaviour. Secondary outcomes are relationships and life skills. A search strategy has been developed that covers eleven databases of published literature in multiple languages. Unpublished literature will also be searched. A meta-analysis will be undertaken if identified studies are suitably heterogenous. Risk of bias will be assessed using tools appropriate to the study methodology. Outcomes across studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology.Discussion:Previous reviews were unable to identify any programs or interventions, backed by methodologically rigorous research, that improve outcomes for this population. This review seeks to update this previous work, taking into account changes in the provision of extended care, which is now available in some jurisdictions. Trial Registration:PROSPERO: CRD42020146999
Comparison of the Quality of life in Patients with Early and Established Rheumatoid Arthritis
Authors: Sizova Lyudmila 
Published: December 2020

Abstract
Aim: To compare the quality of life (QOL) in patients with early rheumatoid arthritis (RA) against patients with established RA.Methods: The clinical study included 164 participants from Russia: 114 outpatients with early RA, and 50 outpatients with established RA. Assessment of QOL in RA patients detected impaired indicators of the HAQ, SF-36 questionnaires, QOL-RA Scale already during the first year of the disease.Results: The HAQ test found a comparable frequency of severe functional disorders in patients with early and established RA. According to the SF-36 questionnaire, patients with early RA suffered from physical pain than patients with established RA. The QOL-RA Scale demonstrated that patients with initial stages of the disease process had the lowest scores for the "arthritis" and "joint pain", and participants with established RA additionally and on the "health".Conclusions: A comparative study of the QOL in respondents with early and established RA has shown that patients have a decrease it already during the first year of the disease on many indicators, as patients with a long anamnesis, and even experience more pronounced physical pain. So, tested questionnaires can provide benefits for monitoring health status and comparison of the effectiveness of drugs and treatment methods.
Potential Metabolic Resistance Mechanisms to Ivermectin in Anopheles Gambiae: A Synergist Bioassay Study
Authors: Nicolas Patricia , Kiuru Caroline , Wagah Martin , Muturi Martha , Duthaler Urs , Hammann Felix , Maia Marta , Chaccour Carlos 
Published: December 2020

Abstract
Background Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively. Methods We determined the lethal-concentration 50 for ivermectin in colonized Anopheles gambiae, then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification. Results Dual inhibition of xenobiotic pumps and cytochromes have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin.Conclusion there is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin.
Analyzing the Genetic Characteristics of a Tryptophan-overproducing Escherichia Coli
Authors: Ding Dongqin , Bai Danyang , Li Jinlong , Mao Zhitao , Zhu Yaru , Liu Pi , Lin Jianping , Ma Hongwu , Zhang Dawei 
Published: December 2020

Abstract
Background: L-tryptophan (L-trp) production in Escherichia coli has been developed by employing random mutagenesis and selection for a long time, but this approach produces an unclear genetic background. Results: We generated the L-trp overproducer TPD5 by combining an intracellular L-trp biosensor and fluorescence-activated cell sorting (FACS) in E. coli, and succeeded in elucidating the genetic basis for L-trp overproduction. The most significant identified positive mutations affected TnaA (deletion), AroG (S211F), TrpE (A63V), and RpoS (nonsense mutation Q33*). The underlying structure-function relationships of the feedback-resistant AroG (S211F) and TrpE (A63V) mutants were uncovered based on protein structure modeling and molecular dynamics simulations, respectively. According to transcriptomic analysis, the global regulator RpoS not only has a great influence on cell growth and morphology, but also on carbon utilization and the direction of carbon flow. Finally, by balancing the concentrations of the L-trp precursors serine and glutamine based on the above analysis, we further increased the titer of L-trp to 3.18 g/L with a yield of 0.18 g/g. Conclusions: The analysis of the genetic characteristics of an L-trp overproducing E. coli provides valuable information on L-trp synthesis and elucidates the phenotype and complex cellular properties in a high-yielding strain, which opens the possibility to transfer beneficial mutations and reconstruct an overproducer with a clean genetic background.
An Optimized Growth Medium for Increased Recombinant Protein Secretion Titer via the Type III&nbsp;Secretion System
Authors: Burdette Lisa , Wong Han Teng , Tullman-Ercek Danielle 
Published: December 2020

Abstract
BackgroundProtein secretion in bacteria is an attractive strategy for heterologous protein production because it retains the high titers and tractability of bacterial hosts while simplifying downstream processing. Traditional intracellular production strategies require cell lysis and separation of the protein product from the chemically similar cellular contents, often a multi-step process that can include an expensive refolding step. The type III secretion system of Salmonella enterica transports proteins from the cytoplasm to the extracellular environment in a single step and is thus a promising solution for protein secretion in bacteria. Product titer is sensitive to extracellular environmental conditions, however, and is therefore not robust. We investigated growth medium composition to provide a favorable environment for secretion that produces consistently high secretion titers, advancing the type III secretion system as a heterologous protein production platform.ResultsWe investigated the effect of carbon sources, buffers, and salts in a rich nutrient base on secretion titer. Carbon sources alone decreased secretion titer, secretion titer increased with salt concentration, and the combination of a carbon source, buffer, and high salt concentration had a synergistic effect on secretion titer. Transcriptional activity measured by flow cytometry showed that medium composition affected secretion system activity, and prolonged secretion system activation correlated strongly with increased secretion titer. We found that an optimal combination of glycerol, phosphate, and sodium chloride provided at least a fourfold increase in secretion titer for a variety of proteins. Further, the increase in secretion titer provided by the optimized medium was additive with strain enhancements.ConclusionsWe leveraged the sensitivity of the type III secretion system to the extracellular environment to increase heterologous protein secretion titer. Our results suggest that maximizing secretion titer via the type III secretion system is not as simple as maximizing secreted protein expression—one must also optimize secretion system activity. This work advances the type III secretion system as a platform for heterologous protein secretion in bacteria and will form a basis for future engineering efforts.
Suboptimal Antiretroviral Drug Levels and Virologic Failures among PLHIV at a Rural Referral Hospital in South Western Uganda: A Descriptive Cross-sectional Study.
Authors: Twinomujuni Silvano Samba , Ogwang Patrick E. , Roelofsen Felicitas , Mukonzo Jackson K. , Atukunda Esther Cathyln 
Published: December 2020

Abstract
Background: Achieving favorable HIV treatment outcomes is a major challenge, particularly due to non-adherence and consequent sub-therapeutic plasma antiretroviral drug levels. This is often complicated by the development of resistant strains due to mutations. Monitoring antiretroviral drug levels in the blood of patients enrolled on ART can reveal if levels are too high, enough, or too low. High levels may lead to dose-dependent side effects and sub-therapeutic levels could promote treatment failure and resistance. In Uganda, as part of routine HIV care, plasma antiretroviral drug level is estimated indirectly by clinic-based pill counts and patient self-reported adherence, which give no evidence of ingested medication. This study aimed at exploring steady-state nevirapine and efavirenz drug levels in HIV patients accessing ART at a rural referral hospital in South Western Uganda. Methods: This study was nested into a randomized clinical trial that evaluated the effect of Artemisia annua L. and Moringa oleifera on immunological response and viral load among persons living with HIV (PLHIV). In the parent study, 250 HIV-infected patients with continued immunologic suppression (CD4 count < 350cells/µL) despite a minimum of one-year on ART were enrolled. Out of 250 clinical trial participants, 95 were randomly selected for steady-state efavirenz and nevirapine plasma concentration sampling having taken the last at bedtime. Additionally, CD4 count, HIV load, liver, and renal function tests were determined. Participants were also interviewed for adherence, and factors that affect blood drug levels.Results: Of the 95 participants sampled, 67 (71%) and 28 (30%) were on efavirenz or nevirapine based ART respectively. The median viral load for participants on the efavirenz regimen was 490 copies/mL (IQR 116, 1900) while that for the participants on the nevirapine regimen was 500 copies/mL (IQR 137, 1270). The median plasma level for the participants on the nevirapine regimen (6.56 mg/L IQR 4.50, 9.80) was higher than that for the participants on the efavirenz regiment (2.54 mg/L IQR 1.47, 5.12). The prevalence of virologic failure among participants sampled on the efavirenz regimen was higher (37%) compared to that of the participants on the nevirapine regimen (21%). 30% of all plasma samples tested had sub-therapeutic levels of either efavirenz or nevirapine, including 2% in which no drugs were detected.Conclusion: Periodic therapeutic drug monitoring should be incorporated as one of the components in the monitoring of ART adherence to ensure adequate blood levels among adults accessing ART at MRRH, SW Uganda.