bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between long-term exposure to air pollutants and cardiopulmonary mortality rates in South Korea
Authors: Hwang Jeongeun , Kwon Jinhee , Yi Hahn , Bae Hyun-Jin , Jang Miso , Kim Namkug
Published: June 2020

Background: The association between long-term exposure to air pollutants, including nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), and particulate matter 10 μm or less in diameter (PM10), and mortality by ischemic heart disease (IHD), cerebrovascular disease (CVD), pneumonia (PN), and chronic lower respiratory disease (CLRD) is unclear. We investigated whether living in an administrative district with heavy air pollution is associated with an increased risk of mortality by the diseases through an ecological study using South Korean administrative data over 19 years. Methods: A total of 249 Si-Gun-Gus, unit of administrative districts in South Korea were studied. In each district, the daily concentrations of CO, SO2, NO2, O3, and PM10 were averaged over 19 years (2001–2018). Age-adjusted mortality rates by IHD, CVD, PN and CLRD for each district were averaged for the same study period. Multivariate beta-regression analysis was performed to estimate the associations between air pollutant concentrations and mortality rates, after adjusting for confounding factors including altitude, population density, higher education rate, smoking rate, obesity rate, and gross regional domestic product per capita. Associations were also estimated for two subgrouping schema: Capital and non-Capital areas (77:172 districts) and urban and rural areas (168:81 districts). Results: For IHD, higher SO2 concentrations were significantly associated with a higher mortality rate, whereas other air pollutants had null associations. For CVD, SO2 and PM10 concentrations were significantly associated with a higher mortality rate. For PN, O3 concentrations had significant positive associations with a higher mortality rate, while SO2, NO2, and PM10 concentrations had significant negative associations. For CLRD, O3 concentrations were associated with an increased mortality rate, while CO, NO2, and PM10 concentrations had negative associations. In the subgroup analysis, positive associations between SO2 concentrations and IHD mortality were consistently observed in all subgroups, while other pollutant-disease pairs showed null, or mixed associations.Conclusion: Long-term exposure to high SO2 concentration was significantly and consistently associated with a high mortality rate nationwide and in Capital and non-Capital areas, and in urban and rural areas. Associations between other air pollutants and disease-related mortalities need to be investigated in further studies.
Validation of a SPANISH version of the Health-Related Quality of Life (HRQoL) measure for Chronic Otitis Media (COMQ-12)
Authors: Otoya-Tono Ana M. , Pérez-Herrera Lucía C. , Peñaranda Daniel , Moreno-López Sergio , Sánchez-Pedraza Ricardo , García Juan Manuel , Phillips John S. , Peñaranda Augusto
Published: June 2020

Background: Evaluation of health-related quality of life (HRQoL) is considered an important aspect of clinical assessment and health research. Chronic Otitis Media (COM) is related to the quality of life deterioration subsequent to COM symptoms, social communication impairments, and lower work performance. However, there is no reliable information regarding the impact of this disease on health and quality of life in many resource-poor countries. Therefore, we translated into Spanish and culturally adapted the Chronic Otitis Media Questionnaire-12 (COMQ-12) for the evaluation of HRQoL of Chronic Otitis Media (COM) in adult patients. Also, we assessed the psychometric properties of the Spanish version of the questionnaire. Methods: Two otology referral centers in Bogotá, Colombia were included. The Spanish version of COMQ-12 was applied twice to 200 adult patients with confirmed COM diagnosis and 31 healthy controls to perform the validation process and assess the internal consistency of this questionnaire. Psychometric characteristics (internal consistency, test-retest reliability, and construct validity) of the COMQ-12 were assessed. Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were conducted via structural equation modeling (SEM) to test the questionnaire’s structure. Results: The Spanish version of the COMQ-12 showed good internal consistency (Cronbach’s Alpha: 0.852, McDonald’s Omega: 0.890). Coefficients corresponding to Lin’s Concordance test and test-retest reliability were 0.945 and 0.825 respectively. Correlation between the Visual Analogue Scale (VAS) and the COMQ-12 was 0.676 (95% CI: 0.593; 0.745) . Factor analysis of the Spanish version of the COMQ-12 indicated a questionnaire structure with three domains: smelly discharge related symptoms; hearing loss related symptoms; and impact on work, lifestyle, and health services . Conclusion: This Spanish version of the COMQ-12 showed high reliability and high internal consistency. This questionnaire can be used as an objective clinical tool to assess the HRQoL of patients who have a COM diagnosis. Trial registration Not applicable. Key Words: Chronic Suppurative Otitis Media, Health-Related Quality of Life, COMQ-12, validity.
Comparing Clinical Outcomes of Piperacillin-Tazobactam Administration and Dosage Strategies in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis
Authors: Fawaz Sarah , Barton Stephen , Nabhani-Gebara Shereen
Published: June 2020

Background: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Methods: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Results: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (Odds Ratio 1.56, 95% Confidence Interval 1.28-1.90, P = 0 .0001), lower mortality rates (Odds Ratio 0.68, 95% Confidence Interval 0.55-0.84, P = 0 .0003), higher microbiological success rates (Odds Ratio 1.52, 95% Confidence Interval 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (Mean Difference -1.27, 95% Confidence Interval -2.45—0.08, P = 0.04) in critically ill patients.Conclusion: Results from this study show that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. However, more rigorous scientific studies in critically ill patients are warranted to reach a sufficient level of evidence and promote further implementation of C/PI as a dosing strategy.
Development and validation of functional markers from Dw1 and Dw2 loci to accurately predict apple rootstock dwarfing ability
Authors: Yang Feng , Shen Fei , Liu Zhi , He Mingli , Wang Yi , Wu Ting , Xu Xuefeng , Li Wei , Qiu Changpeng , Zhang Xinzhong , Han Zhenhai
Published: June 2020

Background: ‘M9’ is a widely used apple dwarfing rootstock due to the outstanding effects on both precocity and vigorous control. Two quantitative trait loci (QTLs), Dw1 and Dw2 , for the dwarfing effect were previously mapped on ‘M9’, but the genetic variations that underpin the dwarfing ability have not been elucidated to date. Result: By using ‘Red Fuji’ trees grafted on 1123 hybrids from ‘ M alus baccata ’ × ‘M9’, the intervals of Dw1 and Dw2 were narrowed down. MdLBD3 and MdARF6 were predicted as potential candidate genes from Dw1 , while MdG3OX3 was a possible candidate gene from Dw2 . An 11 bp deletion at -339 bp upstream of the transcription start site (TSS) of MdLBD3 generated a new cis-element binding site with MdWRKY2 and caused increased expression of MdLBD3 . Coincidently, a ten bp deletion at -278 bp upstream of the TSS of MdG3OX3 created an additional binding site of MdABI5 , leading to higher expression of MdG3OX3 . At -954 bp of the MdARF6 promoter, a 14 bp insertion destroyed the binding ability by MdABI5 and reduced MdARF6 expression. The genotype effects of these insertion and deletions as diagnostic markers on dwarfing traits (tree height, trunk diameter, and canopy width) were estimated in 108 F1 hybrids. The genomic predicted genetic values (GEGV) were calculated by adding up the genotype effects of the three markers and the population mean phenotype. The GEGV of the dwarfing traits exhibited high correlation coefficients of 0.93, 0.94, and 0.93 in terms of tree height, trunk diameter, and canopy width for the observed phenotype values, respectively. The predictability of GEGV was validated in 64 Malus accessions. Conclusion : The development of the three functional markers, Ld/Li, Ad/Ai, and Gd/Gi, ensures the accurate genomic assisted prediction of dwarfing ability in apple rootstock breeding. The data also suggested that ABA, auxin, GA, and zeatin signals may be involved in the regulation of apple rootstock dwarfing mechanism.
Learning Attention for Object Tracking with Adversarial Learning Network
Authors: Cheng Xu , Song Chen , Gu Yongxiang , Chen Beijing
Published: June 2020

Artificial intelligence has been widely studied on solving intelligent surveillance analysis and security problems in recent years. Although many multimedia security approaches have been proposed by using deep learning network model, there are still some challenges on their performances which deserve in-depth research. On one hand, high computational complexity of current deep learning methods makes it hard to be applied to real-time scenario. On the other hand, it is difficult to obtain the specific features of a video by fine-tuning the network online with the object state of the first frame, which fails to capture rich appearance variations of the object. To solve above two issues, in this paper, an effective object tracking method with learning attention is proposed to achieve the object localization and reduce the training time in adversarial learning framework. First, a prediction network is designed to track the object in video sequences. The object positions of the first ten frames are employed to fine-tune prediction network, which can fully mine a specific features of an object. Second, the prediction network is integrated into the generative adversarial network framework, which randomly generates masks to capture object appearance variations via adaptively dropout input features. Third, we present a spatial attention mechanism to improve the tracking performance. The proposed network can identify the mask that maintains the most robust features of the objects over a long temporal span. Extensive experiments on two large-scale benchmarks demonstrate that the proposed algorithm performs favorably against state-of-the-art methods.
Effectiveness of Attachment-Based Family Therapy compared to Treatment as Usual for Depressed Adolescents in Community Mental Health Clinics
Authors: Waraan Luxsiya , Rognli Erling W. , Czajkowski Nikolai Olavi , Aalberg Marianne , Mehlum Lars
Published: June 2020

Background: Major Depressive Disorder (MDD) is a disabling mood disorder, profoundly affecting a large number of adolescent’s quality of life. To date, no obvious treatment of choice for MDD in adolescents is available and progress in the treatment of depressed adolescents will have important public health implications. Attachment-Based Family Therapy (ABFT), as the only empirically supported family therapy model designed to treat adolescent depression, aims to repair interpersonal ruptures and rebuild an emotionally protective parent-child relationship.Objective: To study the effectiveness of ABFT compared with Treatment as Usual (TAU) delivered within child- and adolescent mental health services (CAMHS) to adolescents with MDD.Method: Sixty adolescents (86.7% girls), aged 13-18 years (M = 14.9), with MDD referred to two CAMHS were randomized to receive 16 weeks of ABFT or TAU. ABFT consisted of weekly therapy sessions (family/individual or both) according to the treatment manual. TAU was not monitored. Primary outcomes were clinician-rated (Hamilton Depression Scale, HAMD) and self-reported (Beck Depression Inventory-II, BDI-II) depressive symptoms assessed at baseline and post-treatment by blinded evaluators for HAMD and at baseline, and after 4, 6, 8, 10,12, 14, and 16 weeks for BDI-II. Analyses were performed according to intent-to-treat principles.Results: At post-treatment, clinician-rated remission rates on the HAMD (5 % in ABFT and 3.33% in TAU, p =1, OR=1.54, Fisher’s exact test) and self-reported symptoms of depression on the BDI-II did not differ significantly between groups (X2[2, N = 60] =0.06 , p = 0.97). In both treatment groups participants reported significantly reduced depressive symptoms, but the majority(63.3 %) of adolescents were still in the clinical range after 16 weeks of treatment.Conclusion: ABFT was not associated with more favorable outcomes than TAU Remission and response rates were low in both groups, suggesting none of the treatments were effective in treating MDD in adolescents. These findings call for continued efforts to improve treatment for MDD in outpatient clinics. Policies on implementation of evidence based treatments already available are essential. Future research may focus on moderators of and mechanisms for individual differences to treatment response.Trial Registration: Clinicaltrials.gov identifier: NCT01830088https://clinicaltrials.gov/ct2/show/NCT01830088?term=Villab%C3%B8&draw=2&rank=1 Date of registration: April 12, 2013
Feasibility testing of a community dialogue approach for promoting the uptake of family planning and contraceptive services in Zambia
Authors: Munakampe Margarate Nzala , Nkole Theresa , Silumbwe Adam , Zulu Joseph Mumba , Cordero Joanna Paula , Steyn Petrus S
Published: June 2020

Background: Community dialogues have been used in participatory approaches in various health prevention and awareness programs, including family planning interventions to increase understanding and alignment of particular issues from different peoples’ perspectives. The main aim of this paper is to document the feasibility testing of a community dialogue approach, which aimed to promote dialogue between healthcare providers and community members. The feasibility testing was part of formative-phase research needed to design an intervention, with the ultimate goal of increasing the uptake of family planning and contraception. The community dialogue intervention generated discussions on key approaches to improve family planning and contraception provision and uptake.Methods: Key stages of the community dialogue were undertaken, with representation from healthcare providers and community members. Participants included frontline and managerial health care providers, community health workers, family planning and contraception users, the youth, other stakeholders from the education sector, and civil society. How the dialogue was implemented (operational feasibility) as well as the cultural feasibility of the community dialogue content was evaluated through participant observations during the dialogue, using a standardised feasibility testing tick-list, and through focus group discussions with the stakeholders who participated in the community dialogue.Results: Overall, 21 of the 30 invited participants attended the meeting- 70 per cent attendance. The approach facilitated discussions on how quality care could be achieved in family planning and contraception provision, guided by the ground rules that were agreed upon by the different stakeholders. A need for more time for the discussion was noted. Also, more balanced representation from the adolescents, other stakeholders in family planning such as the community members was noted, especially in comparison to the healthcare providers. Some participants were not comfortable with the language used. And the young people felt older participants used complicated terminologies.Conclusion: Generally, the community dialogue was well received by the community members and the healthcare providers, as was observed from the sentiments expressed by both categories. Some key considerations for refining the approach included soliciting maximum participation from otherwise marginalized groups like the youth would provide stronger representation.
Biofilm formation on three different endotracheal tubes: A prospective clinical trial
Authors: Thorarinsdottir Hulda Rosa , Kander Thomas , Holmberg Anna , Petronis Sarunas , Klarin Bengt
Published: June 2020

Background: Biofilm formation on endotracheal tubes (ETTs) is an early and frequent event in mechanically ventilated patients. The biofilm is believed to act as a reservoir for infecting microorganisms and thereby contribute to development and relapses of ventilator-associated pneumonia (VAP). Once a biofilm has formed on an ETT surface, it is difficult to eradicate. This clinical study aimed to compare biofilm formation on three widely used ETTs with different surface properties and to explore factors potentially predictive of biofilm formation.Methods: We compared the grade of biofilm formation on ETTs made of uncoated polyvinyl chloride (PVC), silicone-coated PVC, and PVC coated with noble metals after > 24 hours of mechanical ventilation in critically ill patients. The comparison was based on scanning electron microscopy of ETT surfaces, biofilm grading, surveillance and biofilm cultures, and occurrence of VAP.Results: High-grade (score ≥ 7) biofilm formation on the ETTs was associated with development of VAP (OR 4.17 [95% CI 1.14–15.3], p = 0.031). Compared to uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation (OR 0.18 [95% CI 0.06–0.59], p = 0.005, and OR 0.34 [95% CI 0.13–0.93], p = 0.036, respectively). No significant difference was observed between silicon-coated ETTs and noble-metal-coated ETTs (OR 0.54 [95% CI 0.17–1.65], p = 0.278). In 60% of the oropharyngeal cultures and 58% of the endotracheal cultures collected at intubation, the same microorganism was found in the ETT biofilm at extubation. In patients who developed VAP, the causative microbe remained in the biofilm in 56% of cases, despite appropriate antibiotic therapy. High-grade biofilm formation on ETTs was not predicted by either colonization with common VAP pathogens in surveillance cultures or duration of invasive ventilation.Conclusion: High-grade biofilm formation on ETTs was associated with development of VAP. Compared to the uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation. Further research on methods to prevent, monitor, and manage biofilm occurrence is needed.Trial registration: ClinicalTrials.gov, NCT02284438. Retrospectively registered on 21 October 2014, URL: https://clinicaltrials.gov/ct2/show/NCT02284438.
Study on the ability of 3D gamma analysis and bio-mathematical model in detecting dose changes caused by dose-calculation-grid-size (DCGS)
Authors: Bai Han , Zhu Sijin , Wu Xingrao , Liu Xuhong , Chen Feihu , Yan Jiawen
Published: June 2020

Objective: To explore the efficacy and sensitivity of 3D gamma analysis and bio-mathematical model for cervical cancer in detecting dose changes caused by dose-calculation-grid-size (DCGS).Methods：17 patients’ plans for cervical cancer were enrolled (Pinnacle TPS，VMAT), and the DCGS was changed from 2.0mm to 5.0mm to calculate the planned dose respectively. The dose distribution calculated by DCGS = 2.0mm as the “reference” data set (RDS), the dose distribution calculated by the rest DCGS as the“measurement”data set (MDS), the 3D gamma passing rates and the (N)TCPs of the all structures under different DCGS were obtained, and then analyze the ability of 3D gamma analysis and (N)TCP model in detecting dose changes and what factors affect this ability.Results: The effect of DCGS on planned dose was obvious. When the gamma standard was 1.0mm, 1.0% and 10.0%, the difference of the results of the DCGS on dose-effect could be detected by 3D gamma analysis (all p value < 0.05). With the decline of the standard, 3D gamma analysis’ ability to detect this difference shows weaker. When the standard was 1.0mm, 3.0% and 10.0%, the p value of > 0.05 accounted for the majority. With DCGS=2.0mm being RDS, ∆gamma-passing-rate presented the same trend with ∆(N)TCPs of all structures except for the femurs only when the 1.0mm, 1.0% and 10.0% standards were adopted for the 3D gamma analysis.Conclusions: The 3D gamma analysis and bio-mathematical model can be used to analyze the effect of DCGS on the planned dose. For comparison, the former’s detection ability has a lot to do with the designed standard, and the latter’s capability is related to the parameters and calculated accuracy instrinsically.
Positive results for patients with COVID-19 discharged form hospital in Chongqing, China
Authors: Deng Wang , Guang Tian-wen , Yang Mei , Li Jian-rong , Jiang De-peng , Li Chang-yi , Wang Dao-Xin
Published: June 2020

Background: Since December 2019, over 80,000 patients with coronavirus disease 2019 (COVID-19) have been confirmed in China. With the increasing number of recovered patients, more attention should be paid to the follow-up of these patients. Methods: In the study, 576 patients with COVID-19 discharged from hospital in Chongqing, China from January 24, 2020, to March 10, 2020 were evaluated by viral nucleic acid tests for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) to determine if they could be released from quarantine. Among the 576 patients, 61 patients (10.6%) had positive RT-PCR test results of SARS-CoV-2. We aimed to analyze the demographics, clinical characteristics and treatment of 61 patients.Results: These positive patients were characterized by older age, chronic medical illness and mild conditions. 38 (62.3%) patients who were asymptomatic without abnormalities on chest radiographs were found in the positive with COVID-19. Also, they showed positive results of stool or sputum specimens with negative results of nasal and pharyngeal swab specimens. The median duration of positive result of SARS-CoV-2 was varied from 3 days to 35 days in the patients discharged from hospital with no family member infection. Conclusions: Multi-site screening of SARS-CoV-2 including nasal and pharyngeal swabs, stool and sputum specimens could be considered to improve the diagnosis, treatment and infection control in patients with COVID-19. Our findings provide the important information and clinical evidence for the improved management of patients recovered from COVID-19
Dynamic Simulation of Continuous Mixed Sugar Fermentation with Increasing Cell Retention Time for Lactic Acid Production using Enterococcus mundtii QU 25
Authors: Wang Ying , Chan Ka-Lai , Abdel-Rahman Mohamed Ali , Sonomoto Kenji , Leu Shao-Yuan
Published: June 2020

Background: The simultaneous and effective conversion of both pentose and hexose in fermentation is a critical and challenging task towards the lignocellulosic economy. This study aims to investigate the feasibility of an innovative co-fermentation process featuring with a cell recycling unit (CF/CR) for mixed sugar utilization. A l-lactic acid producing strain Enterococcus mundtii QU 25, was applied in the continuous fermentation process, and the mixed sugars were utilized at different productivities after the flowing conditions were changed. A numerical platform was constructed with the experiments to optimize the biological process and clarify the cell metabolism through kinetics analysis. The structured model, kinetic parameters, and achievement of the fermentation strategy shall provide new insights towards whole sugar fermentation via real-time monitoring for process control and optimization. Results: Significant carbon catabolite repression in co-fermentation using a glucose/xylose mixture was overcome by replacing glucose with cellobiose, and the ratio of consumed pentose to consumed hexose increased significantly from 0.096 to 0.461 by mass. An outstanding product concentration of 65.2 g·L-1 and productivity of 13.03 g·L-1·h-1 were achieved with 50 g·L-1 cellobiose and 30 g·L-1 xylose at an optimized dilution rate of 0.2 h-1, and the cell retention time gradually increased. Among the total lactic acid production, xylose contributed to more than 34% of the mixed sugars, which was close to the related contents in agricultural residuals. The model successfully simulated the transition of sugar consumption, cell growth, and lactic acid production among the batch, continuous process, and CF/CR systems. Conclusion: Cell retention time played a critical role in balancing pentose and hexose consumption, cell decay, and lactic acid production in the CF/CR process. With increasing cell concentration, consumption of mixed sugars increased with the productivity of the final product; hence, the impact of substrate inhibition was reduced. With the validated parameters, the model showed the highest accuracy simulating the CF/CR process, and significantly longer cell retention times compared to hydraulic retention time were tested.
Genetic Effects of Soluble Starch Synthase IV-2 and It with ADPglucose Pyrophorylase Large Unit and Pullulanase on Rice Qualities
Authors: Xu Liang , You Hui , Zhang Ouling , Xiang Xunchao
Published: June 2020

Background: Rice amylose content and amylopectin structure corporately determine rice eating and cooking qualities (ECQs). Soluble starch synthase ( SS ) IV-2 is a member of the soluble starch synthesis gene family but with unknown effects on ECQs. Results: In this study, three populations derived from a cross of two parents who possess the same major genes of starch bio-synthesis were employed to investigate the influence of SSIV-2 and its combined effects with ADPglucose pyrophorylase large unit ( AGPlar ) and Pullulanase ( PUL ) on ECQs. The results illustrated that the polymorphism of SSIV-2 alleles significantly affected gel consistency (GC), gelatinization temperature (GT), percent of retrogradation (PR) and three crucial rapid viscosity analysis (RVA) profile parameters: peak viscosity (PKV), breakdown viscosity (BDV) and setback viscosity (SBV). And SSIV-2 allele derived from CG173R had better quality traits with lower GT, SBV and PR. Moreover, its interaction with AGPlar was responsible for the variations of GC, apparent amylose content (AAC), GT, PR and all RVA parameters except for pasting temperature (PaT) and peak time (PeT), in terms of GC, PKV and CSV, AGPlar derived from CG173R had an epistatic effect on SSIV-2 ; additionally, interaction of SSIV-2 and PUL mainly affected GC, AAC, PKV, CPV, CSV and SBV. I-C and C-1 (I, allele of AGPlar from Guangzhan 63S; C, allele of SSIV-2 from CG173R; 1, allele of PUL from Guangzhan 63S) combinations had better ECQs. Conclusions: SSIV-2 alleles significantly affect rice quality, especially the parameters relevant to gelatinized and thermal characteristics of starch (GC, PR, GT, PKV, BDV and SBV) under the same major genes ( Waxy and SSII-3 ) background. It indicates that SSIV-2 functions elongation of starch chain. These findings suggest that the effects of SSIV-2 and its interaction with AGPlar and PUL are vital for rice quality breeding with the same major genes.
GENOME-WIDE SCAN FOR COMMON VARIANTS ASSOCIATED WITH INTRAMUSCULAR FAT AND MOISTURE CONTENT IN RAINBOW TROUT
Authors: Ali Ali R. , Al-Tobasei Rafet , Lourenco Daniela , Leed Tim , Kenney Brett , Salem Mohamed
Published: June 2020

Background Genetic improvement of fillet quality attributes is a priority of the aquaculture industry. Muscle composition impacts quality attributes such as flavor, appearance, texture, and juiciness. Fat and moisture make up about ~80% of the tissue weight. The genetic architecture underlying the fat and moisture content of the muscle is still to be fully explored in fish. A 50K gene transcribed SNP chip was used for genotyping 789 fish with available phenotypic data for fat and moisture content. Genotyped fish were obtained from two consecutive generations produced in the National Center for Cool and Cold Water Aquaculture (NCCCWA) growth-selective breeding program. Estimates of SNP effects from weighted single-step GBLUP (WssGBLUP) were used to perform genome-wide association (GWA) analysis to identify quantitative trait loci (QTL) associated with the studied traits. Results Using genomic sliding windows of 50 adjacent SNPs, 137 and 178 SNPs were identified as associated with fat and moisture content, respectively. Chromosomes 19 and 29 harbored the highest number of SNPs explaining at least 2% of the genetic variation in fat and moisture content. A total of 61 common SNPs on chromosomes 19 and 29 affected the aforementioned traits; this association suggests common mechanisms underlying intramuscular fat and moisture content. Additionally, based on single-marker GWA analyses, 8 and 24 SNPs were identified in association with fat and moisture content, respectively. Conclusion SNP-harboring genes were primarily involved in lipid metabolism, cytoskeleton remodeling, and protein turnover. This work provides putative SNP markers that could be prioritized and used for genomic selection in breeding programs.
Onset features and time to diagnosis in Friedreich´s Ataxia
Authors: Indelicato Elisabetta , Nachbauer Wolfgang , Eigentler Andreas , Amprosi Matthias , Gothe Raffaella Matteucci , Giunti Paola , Mariotti Caterina , Arpa Javier , Durr Alexandra , Klopstock Thomas , Schöls Ludger , Giordano Ilaria , Bürk Katrin , Pandolfo Massimo , Didszdun Claire , Schulz Jörg , Boesch Sylvia
Published: June 2020

Background: In rare disorders diagnosis may be delayed due to limited awareness and unspecific presenting symptoms. Herein, we address the issue of diagnostic delay in Friedreich´s Ataxia (FRDA), a genetic disorder usually caused by homozygous GAA-repeat expansions. Methods: 611 genetically confirmed FRDA patients were recruited within a multicentric natural history study conducted by the EFACTS (European FRDA Consortium for Translational Studies, ClinicalTrials.gov-Identifier NCT02069509). Age at first symptoms as well as age at first suspicion of FRDA by a physician were collected retrospectively at the baseline visit. Results: In 554 of cases (90.7%), disease presented with gait or coordination disturbances. In the others (n=57, 9.3%), non-neurological features such as scoliosis or cardiomyopathy predated ataxia. Before the discovery of the causal mutation in 1996, median time to diagnosis was 4(IQR=2-9) years and it improved significantly after the introduction of genetic testing (2(IQR=1-5) years, p<0.001). Still, after 1996, time to diagnosis was longer in patients with a) non-neurological presentation (mean 6.7, 95%CI[5.5,7.9] vs 4.5, [4.2,5] years in those with neurological presentation, p=0.001) as well as in b) patients with late-onset (3(IQR=1-7) vs 2(IQR=1-5) years compared to typical onset <25 years of age, p=0.03). Age at onset significantly correlated with the length of the shorter GAA repeat (GAA1) in case of neurological onset (r=-0,6; p<0,0001), but not in patients with non-neurological presentation (r=-0,1; p=0,4). Across 54 siblings’ pairs, differences in age at onset did not correlate with differences in GAA-repeat length (r=-0,14, p=0,3).Conclusions: In the genetic era, presentation with non-neurological features or in the adulthood still leads to a significant diagnostic delay in FRDA. Well-known correlations between GAA1 repeat length and disease milestones are not valid in case of atypical presentations or positive family history.
Up-regulation of miR-1825 inhibits the progression of glioblastoma by suppressing CDK14 though Wnt/β-catenin signaling pathway
Authors: Lu Fengqin , Li Chunhong , Sun Yuping , Jia Ting , Li Na , Li Haiyan
Published: June 2020

Background: Mounting evidences displayed that miRNAs play crucial roles in tumor initiation and development. However, the regulation and relevant mechanism of miR- miR-1825 in glioblastoma (GBM) remain unclear. Methods: qRT-PCR was used to detect miR-1825 and CDK14 mRNA expression. Western blot was applied for testing protein levels (VEGF, E-cadherin, N-cadherin, vimentin, β-catenin, c-myc, p-c-Jun). MTT and transwell assays were used for detecting GBM cell progression, including cell viability, migration, and invasion.Results: The results showed that miR-1825 was decreased in GBM tissue specimens by qRT-PCR and it was confirmed as a prognostic marker of GBM by Kaplan-Meier survival analysis. Moreover, we also found that miR-1825 up-regulation suppressed GBM cell viability, tumor growth, invasion and migration. Furthermore, CDK14 was first identified as the direct target of miR-1825 by Luciferase reporter assay. CDK14 acted as an oncogene in GBM development by Immunohistochemistry. In addition, Western blot analysis demonstrated that miR-1825 regulated Wnt/β-catenin signaling pathway in GBM development. Conclusion: In conclusion, miR-1825 up-regulation suppressed GBM progression by targeting CDK14 through Wnt/β-catenin pathway.
Erenumab in highly therapy-refractory migraine patients: First German Real-world evidence
Authors: Scheffler Armin , Messel Olga , Wurthmann Sebastian , Nsaka Michael , Kleinschnitz Christoph , Glas Martin , Naegel Steffen , Holle-Lee Dagny
Published: June 2020

Background: Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAB) are the first specific migraine prophylactic medication. Erenumab is the only CGRP mAB targeting the CGRP receptor. Clinical data regarding efficacy and tolerability of erenumab in highly therapy-refractory patients are not available, yet, although many patients treated with CGRP mAB under real world conditions can be considered as highly therapy-refractory.Methods: Clinical routine data of highly therapy-refractory migraine patients treated with erenumab 70mg for three months between November 2018 and December 2019 in the West German Headache Center, University Hospital Essen, Germany, were analysed. Monthly migraine days (MMD), monthly headache days (MHD) and days of acute medication intake (AMD) were assessed. Statistical analysis was performed using the Wilcoxon test. Descriptive statistics were performed to evaluate changes of vegetative symptoms, acute medication response, side effects, as well as treatment satisfaction.Results: Complete clinical data were available for 26 episodic (EM) and 74 chronic (CM) migraineurs. Sixty-six % (n=49) of CM patients had an additional medication overuse headache (MOH). After three months 57.7 % of EM patients and 41.9 % of CM patients had a 50% or greater reduction of MMD. The mean number of MMD was reduced by 3.43 (SE 1.26) in EM, and by 4.72 (SE 0.87) in CM. Thirty-nine patients (52.7%) returned from chronic to episodic course of migraine. After three months, 23 patients (46.9%) were not suffering from a MOH anymore.Conclusions: Erenumab seems to be a promising therapeutic option in highly therapy-refractory migraine patients.Trial registration: Retrospective registered.
Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery
Authors: Zhang Xiaojing , Lv Zunfu , Xu Xiaoxian , Yin Zhuomin , Lou hanmei
Published: June 2020

Background: To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy. Methods. We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis. Results: Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) > 5 ng/ml (p=0.049 and p=0.013, respectively); moreover, they were much older (P=0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) > 5 ng/ml and SCC-Ag > 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS (P=0.036 and P=0.047, respectively). Conclusions: We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.
Aquatic habitats of the malaria vector, Anopheles funestus in rural south-eastern Tanzania
Authors: Nambunga Ismail Hassani , Ngowo Halfan S. , Mapua Salum A. , Hape Emmanuel E. , Msugupakulya Betwel J. , Msaky Dickson S. , Mhumbira Nicolaus T. , Mchwembo Karim R. , Tamayamali Gerald Z. , Mlembe Slyakus V. , Njalambaha Rukiyah M. , Lwetoijera Dickson W. , Finda Marceline F. , Govella Nicodem J. , Matoke-Muhia Damaris , Kaindoa Emmanuel W. , Okumu Fredros O.
Published: June 2020

Background: In rural south-eastern Tanzania, Anopheles funestus are a major malaria vector, and have been implicated in nearly 90% of infective bites. However, little is known about the natural ecological requirements and survival strategies of this mosquito species.Methods: Potential mosquito aquatic habitats were systematically searched along 1000 m transects radiating from the centres of six villages in south-eastern Tanzania. All water bodies were geo-referenced, characterized and examined for presence of Anopheles larvae using standard 350mls dippers or 10L buckets. Larvae were collected for rearing, and the emergent adults identified to generic or species level, to confirm habitats containing An. funestus. Results: One hundred and eleven (111) habitats were identified and assessed from the first five villages (all <300m altitude). Of these, 36 (32.4%) had An. funestus larvae co-occurring with other mosquito species. Another 47 (42.3%) had other Anopheles species and/or culicines but not An. funestus, and 28 (25.2%) had no mosquitoes. There were three main habitat types occupied by An. funestus, namely: a) small spring-fed pools with well-defined perimeters (36.1%), b) medium-sized natural ponds retaining water most of the year (16.7%), and c) slow-moving waters along river tributaries (47.2%). The habitats generally had clear waters with emergent surface vegetation, depths > 0.5m and distances < 100m from human dwellings. They were permanent or semi-permanent, retaining water most of the year. Water temperatures ranged from 25.2 to 28.8°C, pH from 6.5 to 6.7, turbidity from 26.6 to 54.8 NTU and total dissolved solids from 60.5 to 80.3 mg/L. In the sixth village (altitude >400m), very high densities of An. funestus were found along rivers with slow-moving clear waters and emergent vegetation.Conclusion: This study has documented the diversity and key characteristics of aquatic habitats of An. funestus in south-eastern Tanzania, and will form an important basis for further ecological studies towards improved control strategies. Given the observed characteristics, An. funestus habitats in the area can indeed be described as fixed, few and findable. Future studies should therefore investigate potential of targeting these habitats with larviciding or larval source management to complement malaria control efforts in areas dominated by this vector.
Investigation of Pindan Soil Modified with Polymer Stablisers for Road Pavement
Authors: PARK HYUN KYU , Lee Hyuk , Vimonsatit Vanissorn
Published: June 2020

Road failures are often caused by structural weaknesses, and particularly unsealed roads are vulnerable to water as water easily flows into road structures. Moisture susceptibility of materials is an important aspect when pavements are designed as moisture can weaken bonds between aggregates. Pindan soil is a red soil, known as a soft and moisture sensitive soil. Polymer stabilisers have been proved that they can improve soil mechanical properties by providing an internal waterproofing. Studies of the polymer-Pindan soil stabilisation have been focused on engineering performances, but literature shows little information on the fundamental information of Pindan soil. This project focuses on fundamental information of Pindan soil and its improved performances using polymer stabilisers. Plastic index, specific gravity and particle size distribution were tested to obtain the basic properties. Compaction, Unconfined Compressive Strength and California Bearing Ratio tests were performed to determine the mechanical properties. The chemical property was examined using X-ray diffraction. Furthermore, the waterproof effect of the polymers on the stabilised Pindan soil was investigated from capillary rise tests. In addition, the mechanical properties of individual soil grains were investigated using nanoindentation tests. The materials used for this investigation primarily consisted of Pindan soil collected in Broome, Western Australia, and three polymer products manufactured in Australia. Based on the results, it is evident that the failure behaviour, strain and strength as well as the basic properties of the soils are affected and changed by the Polymer stabilisers. The type of polymer influenced the optimum moisture contents and strengths rather than the amount of polymer. Similarly, Nanoindentation technology provided various information such as elastic modulus, hardness, packing density, stiffness, cohesion and fracture toughness of soils at nano-scales. Polymers can reduce water ingress and minimise moisture in the pavement structures. Thus, the structures can maintain its strength and prevent deformation, which will increase the lifetime of unsealed pavements.
Development of calcium stabilized nitrogen rich alpha-sialon ceramics along the Si3N4:1/2Ca3N2:3AlN line using spark plasma sintering
Authors: Ahmed Bilal Anjum , Hakeem Abbas Saeed , Laoui Tahar
Published: June 2020

Calcium stabilized nitrogen rich sialon ceramics having a general formula of CaxSi12-2xAl2xN16 with x value in the range of 0.2-2.2 for compositions lying along the Si3N4:1/2Ca3N2:3AlN line were synthesized using nano/submicron size starting powder precursors and spark plasma sintering (SPS) technique. The development of calcium stabilized nitrogen rich sialon ceramics at a significantly low sintering temperature of 1500°C (typically reported a temperature of 1700°C or greater) remains to be the highlight of the present study. The SPS processed sialons were characterized for their microstructure, phase and compositional analysis, physical and mechanical properties. Furthermore, a correlation was developed between the lattice parameters and the content (x) of the alkaline metal cation in the alpha-sialon phase. Well densified single-phase nitrogen rich alpha-sialon ceramics were achieved in the range of 0.53(3) ≤ x ≤ 1.27(3). A nitrogen rich alpha-sialon sample possessing a maximum hardness of 22.4 GPa and fracture toughness of 6.1 MPa.m1/2 was developed.
Clubfoot treatment with Ponseti method – Parental distress during plaster casting
Authors: Walter Christian , Sachsenmaier Saskia , Wünschel Markus , Teufel Martin , Götze Marco
Published: June 2020

Background Clubfoot is one of the most prevalent musculoskeletal congenital defects. Gold standard treatment of idiopathic clubfoot is the conservative Ponseti method, including the reduction of deformity with weekly serial plaster casting and percutaneous Achilles tenotomy. It is well known that parents of children with severe and chronic illnesses are mentally stressed, but in recent studies regarding clubfoot treatment, parents were only asked about their satisfaction with the treatment. Largely unknown is parental distress before and during plaster casting in clubfoot.Therefore, we want to determinate first, how pronounced the parents' worries are before treatment and if they decrease during the therapy. Second, we hypothesized that parents faced with an extreme deformity (high Pirani-Score), reveal more distress, than parents whose children have a less pronounced deformity (low Pirani-Score). Therefore, we wanted to investigate weather the Pirani score correlates with the parents' mental resilience in relation to the therapy of the child as a global distress parameter.Methods: To answer this question, we developed a questionnaire with the following emphases: Physical capacity, mental resilience, motion score, parents score and child score with point scores 1 (not affected) to 6 (high affected). Subsequently, we interviewed 20 parents whose children were treated with clubfeet and determined the Pirani score of the infants at the beginning (T0) and at the end (TE) of the treatment with plaster casting.Results High values were obtained in child score (Mean (M) = 3.11), motion score (M = 2.63) and mental resilience (M = 2.25). During treatment, mental resilience improved (p = 0.015) significantly. The Spearman correlation coefficient between Pirani-Score (T0) and mental resilience (T0) is 0.21, so the initial hypothesis had to be rejected.Conclusion The issues of the children are in the focus of parental worries concerning clubfoot treatment, especially the assumed future motion and the assumed ability to play with other children. Particular emphasis should be placed on educating parents about the excellent long-term results in the function of the treated feet especially as this topic shows the greatest parental distress.