bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of transgene-free PDS mutants in potato by Agrobacterium-mediated transformation
Authors: Bánfalvi Zsófia , Csákvári Edina , Villányi Vanda , Kondrák Mihály 
Published: May 2020

Abstract
Background
Gene editing using the CRISPR/Cas9 system has become a routinely applied method in several plant species. The most convenient gene delivery system is Agrobacterium-mediated gene transfer with antibiotic selection and stable genomic integration of transgenes, including Cas9. For elimination of transgenes in the segregating progeny, selfing is applied in many plant species. This approach, however, cannot be widely employed in potato because most of the commercial potato cultivars are self-incompatible.

Results
In this study, the efficiency of a transient Cas9 expression system with positive/negative selection based on codA-nptII fusion was tested. The PHYTOENE DESATURASE (PDS) gene involved in carotenoid biosynthesis was targeted. A new vector designated PROGED::gPDS carrying only the right border of T-DNA was constructed. Using only the positive selection function of PROGED::gPDS and the restriction enzyme site loss method in PCR of genomic DNA after digestion with the appropriate restriction enzyme, it was demonstrated that the new vector is as efficient in gene editing as a traditional binary vector with right- and left-border sequences. Nevertheless, 2 weeks of positive selection followed by negative selection did not result in the isolation of PDS mutants. In contrast, we found that with 3-day positive selection, PDS mutants appear in the regenerating population with a minimum frequency of 2–10%. Interestingly, while large deletions (> 100 bp) were generated by continuous positive selection, the 3-day selection resulted in deletions and substitutions of only a few bp. Two albinos and three chimaeras with white and green leaf areas were found among the PDS mutants, while all the other PDS mutant plants were green. Based on DNA sequence analysis some of the green plants were also chimaeras. Upon vegetative propagation from stem segments in vitro, the phenotype of the plants obtained even by positive selection did not change, suggesting that the expression of Cas9 and gPDS is silenced or that the DNA repair system is highly active during the vegetative growth phase in potato.

Conclusions
Gene-edited plants can be obtained from potatoes by Agrobacterium-mediated transformation with 3-day antibiotic selection with a frequency high enough to identify the mutants in the regenerating plant population using PCR.
Effect of a postpartum family planning intervention on postpartum intrauterine device counseling and choice: evidence from a cluster-randomized trial in Tanzania
Authors: Pearson Erin , Senderowicz Leigh , Pradhan Elina , Francis Joel , Muganyizi Projestine , Shah Iqbal , Canning David , Karra Mahesh , Ulenga Nzovu , Bärnighausen Till 
Published: May 2020

Abstract
Background
The World Health Organization recommends postpartum family planning (PPFP) for healthy birth spacing. This study is an evaluation of an intervention that sought to improve women’s access to PPFP in Tanzania. The intervention included counseling on PPFP during antenatal and delivery care and introducing postpartum intrauterine device (PPIUD) insertion as an integrated part of delivery services for women electing PPIUD in the immediate postpartum period.

Methods
This cluster-randomized controlled trial recruited 15,264 postpartum Tanzanian women aged 18 or older who delivered in one of five study hospitals between January and September 2016. We present the effectiveness of the intervention using a difference-in-differences approach to compare outcomes, receipt of PPIUD counseling and choice of PPIUD after delivery, between the pre- and post-intervention period in the treatment and control group. We also present an intervention adherence-adjusted analysis using an instrumental variables estimation.

Results
We estimate linear probability models to obtain effect sizes in percentage points (pp). The intervention increased PPIUD counseling by 19.8 pp (95% CI: 9.1 – 22.6 pp) and choice of PPIUD by 6.3 pp (95% CI: 2.3 – 8.0 pp). The adherence-adjusted estimates demonstrate that if all women had been counseled, we would have observed a 31.6 pp increase in choice of PPIUD (95% CI: 24.3 – 35.8 pp). Among women counseled, determinants of choosing PPIUD included receiving an informational leaflet during counseling and being counseled after admission for delivery services.

Conclusions
The intervention modestly increased the rate of PPIUD counseling and choice of PPIUD, primarily due to low coverage of PPIUD counseling among women delivering in study facilities. With universal PPIUD counseling, large increases in choice of PPIUD would have been observed. Giving women informational materials on PPIUD and counseling after admission for delivery are likely to increase the proportion of women choosing PPIUD.

Trial registration
Registered with clinicaltrials.gov (NCT02718222) on March 24, 2016, retrospectively registered.
Evaluation of neuroprotective and anti-amnesic effects of Elaeagnus umbellata Thunb. On scopolamine-induced memory impairment in mice
Authors: Nazir Nausheen , Zahoor Muhammad , Nisar Mohammad , Karim Nasiara , Latif Abdul , Ahmad Sajjad , Uddin Zia 
Published: May 2020

Abstract
Background
Elaeagnus umbellata is abundantly found in Himalayan regions of Pakistan which is traditionally used to treat various health disorders. However, the experimental evidence supporting the anti-amnesic effect is limited. Therefore the study was aimed to evaluate the prospective beneficial effect of E. umbellata on learning and memory in mice.

Objectives
To assess neuroprotective and anti-amnesic effects of E. umbellata fruit extracts and isolated compounds on the central nervous system.

Methods
Major phytochemical groups present in methanolic extract of E. umbellata were qualitatively determined. The total phenolic and flavonoid contents were also determined in extract/fractions of E. umbellata. On the basis of in vitro promising anticholinesterases (AChE & BChE) and antioxidant activities observed for CHF. Ext and isolated compound-I (Chlorogenic acid = CGA), they were further evaluated for learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Y maze and Novel object recognition using standard procedures. The test sample were further assessed for in vivo anticholinesterases (AChE & BChE) and DPPH free radical scavenging activities in mice brain sample and finally validated by molecular docking study using GOLD software.

Results
The extract/fractions and isolated compounds were tested for their anticholinesterase and antioxidant potentials. The CHF. Ext and CGA showed maximum % inhibition of tested cholinesterases and free radicals. The CHF. Ext and CGA reversed the effects of scopolamine in mice. The CHF. Ext and CGA significantly increased the alternate arm returns and % spontaneous alteration performance while escape latency times (second) significantly decreased in Y maze test. The CHF. Ext and CGA significantly increased the time spent with novel object and also increased the discrimination index in the Novel object recognition test. Furthermore, molecular docking was used to validate the mechanism of cholinesterases inhibition of isolated compounds.

Conclusion
The data obtained from behavioral and biochemical studies (AChE/BChE and DPPH/ABTS inhibition) have shown that E. umbellata possessed significant memory enhancing potency. These results suggest that E. umbellata extract possess potential antiamnesic effects and amongst the isolated compounds, compound I could be more effective anti-amnesic therapeutics. However, further studies are needed to identify the exact mechanism of action.

Graphical abstract
How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study
Authors:   The CENTER-TBI investigators and participants, Timmers Marjolein , van Dijck Jeroen T. J. M. , van Wijk Roel P. J. , Legrand Valerie , van Veen Ernest , Maas Andrew I. R. , Menon David K. , Citerio Giuseppe , Stocchetti Nino , Kompanje Erwin J. O. 
Published: May 2020

Abstract
Background
The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency.

Methods
We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe.

Results
From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75–224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074).

Conclusion
We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.
Actigraphy in brain-injured patients – A valid measurement for assessing circadian rhythms?
Authors: Angerer Monika , Schabus Manuel , Raml Marion , Pichler Gerald , Kunz Alexander B. , Scarpatetti Monika , Trinka Eugen , Blume Christine 
Published: May 2020

Abstract
Background
Actigraphy has received increasing attention in classifying rest-activity cycles. However, in patients with disorders of consciousness (DOC), actigraphy data may be considerably confounded by passive movements, such as nursing activities and therapies. Consequently, this study verified whether circadian rhythmicity is (still) visible in actigraphy data from patients with DOC after correcting for passive movements.

Methods
Wrist actigraphy was recorded over 7–8 consecutive days in patients with DOC (diagnosed with unresponsive wakefulness syndrome [UWS; n = 19] and [exit] minimally conscious state [MCS/EMCS; n = 11]). The presence and actions of clinical and research staff as well as visitors were indicated using a tablet in the patient’s room. Following removal and interpolation of passive movements, non-parametric rank-based tests were computed to identify differences between circadian parameters of uncorrected and corrected actigraphy data.

Results
Uncorrected actigraphy data overestimated the interdaily stability and intradaily variability of patients’ activity and underestimated the deviation from a circadian 24-h rhythm. Only 5/30 (17%) patients deviated more than 1 h from 24 h in the uncorrected data, whereas this was the case for 17/30 (57%) patients in the corrected data. When contrasting diagnoses based on the corrected dataset, stronger circadian rhythms and higher activity levels were observed in MCS/EMCS as compared to UWS patients. Day-to-night differences in activity were evident for both patient groups.

Conclusion
Our findings indicate that uncorrected actigraphy data overestimates the circadian rhythmicity of patients’ activity, as nursing activities, therapies, and visits by relatives follow a circadian pattern itself. Therefore, we suggest correcting actigraphy data from patients with reduced mobility.
High-level production of poly-γ-glutamic acid from untreated molasses by Bacillus siamensis IR10
Authors: Wang Dexin , Kim Hyangmi , Lee Sungbeom , Kim Dae-Hyuk , Joe Min-Ho 
Published: May 2020

AbstractBackgroundPoly-γ-glutamic acid (γ-PGA) is a promising biopolymer and has been applied in many fields.Bacillus siamensisSB1001 was a newly isolated poly-γ-glutamic acid producer with sucrose as its optimal carbon source. To improve the utilization of carbon source, and then molasses can be effectively used for γ-PGA production,60cobalt gamma rays was used to mutate the genes ofB. siamensisSB1001.ResultsBacillus siamensisIR10 was screened for the production of γ-PGA from untreated molasses. In batch fermentation, 17.86 ± 0.97 g/L γ-PGA was obtained after 15 h, which is 52.51% higher than that of its parent strain. Fed-batch fermentation was performed to further improve the yield of γ-PGA with untreated molasses, yielding 41.40 ± 2.01 g/L of γ-PGA with a productivity of 1.73 ± 0.08 g/L/h. An average γ-PGA productivity of 1.85 g/L/h was achieved in the repeated fed-batch fermentation. This is the first report of such a high γ-PGA productivity. The analysis of the enzyme activities showed that they were affected by the carbon sources, enhanced ICDH and GDH, and decreased ODHC, which are important for γ-PGA production.ConclusionThese results suggest that untreated molasses can be used for economical and industrial-scale production of γ-PGA byB. siamensisIR10.
What is needed for implementing drug checking services in the context of the overdose crisis? A qualitative study to explore perspectives of potential service users
Authors: Wallace Bruce , van Roode Thea , Pagan Flora , Phillips Paige , Wagner Hailly , Calder Shane , Aasen Jarred , Pauly Bernie , Hore Dennis 
Published: May 2020

Abstract
Background
The current illicit drug overdose crisis within North America and other countries requires expanded and new responses to address unpredictable and potentially lethal substances, including fentanyl analogues, in the unregulated drug market. Community-wide drug checking is being increasingly explored as one such public health response. We explored how drug checking could be implemented as a potential harm reduction response to the overdose crisis, from the perspective of potential service users.

Methods
The research was guided by the Consolidated Framework for Implementation Research (CFIR). We conducted a qualitative, pre-implementation study to inform development and implementation of drug checking services that are acceptable to people who use substances and meet their needs. University and community researchers conducted 27 in-depth interviews with potential service users at prospective drug checking sites. We inductively developed emerging themes to inform the implementation of drug checking services within the five domains of the CFIR, and identified the most relevant constructs.

Results
Implementing community drug checking faces significant challenges within the current context of criminalization and stigmatization of substance use and people who use/sell drugs, and trauma experienced by potential service users. Participants identified significant risks in accessing drug checking, and that confidential and anonymous services are critical to address these. Engaging people with lived experience in the service can help establish trust. The relative advantage of drug checking needs to outweigh risks through provision of accurate results conveyed in a respectful, non-judgemental way. Drug checking should provide knowledge relevant to using and/or selling drugs and informing one’s own harm reduction.

Conclusions
For service users, the extent to which the implementation of drug checking can respond to and mitigate the risks of being criminalized and stigmatized is critical to the acceptability and success of community drug checking. The culture and compatibility of the service, setting and staff with harm reduction principles and practices is essential.
Psychometric properties of the Connor-Davidson Resilience Scale (CD-RISC) in a non-clinical population in Sweden
Authors: Velickovic Katarina , Rahm Hallberg Ingalill , Axelsson Ulrika , Borrebaeck Carl A. K. , Rydén Lisa , Johnsson Per , Månsson Johanna 
Published: May 2020

Abstract
Background
The Connor-Davidson Resilience Scale (CD-RISC) is the most widely used scale which assesses psychological resilience. Although it is recommended to be applied as a unidimensional scale, its factor structure, reliability, as well as discriminant and predictive validity need to be assessed when used in a new context. Moreover, the original five-factor structure has not been replicated in previous investigations. This study aimed to explore psychometric properties of the scale in a Swedish context.

Methods
Construct validity of the five-factor model of CD-RISC was assessed using Exploratory and Confirmatory Factor Analyses. Its discriminant validity was assessed in relation to a measure of emotion regulation (Brief Version of the Difficulties in Emotion Regulation Scale) using a Confirmatory Factor Analysis. Predictive validity of CD-RISC was assessed in relation to measures of physical and mental health-related quality of life (The 12-Item Short Form Survey) using hierarchical multiple regression analyses. A population based sample cohort was employed (N = 2599).

Results
Exploratory and Confirmatory Factor Analyses suggested a 22-item unidimensional model of CD-RISC. Psychological resilience was found to be independent from the measure of emotion regulation. It was shown to predict both physical and mental health-related quality of life, being especially strongly associated with mental health aspects.

Conclusions
The study showed that the Swedish version of CD-RISC is an instrument with high discriminant and predictive validity, although the original factor structure does not apply in this context. CD-RISC can thus be used to identify individuals with a higher need of psychosocial support, especially relating to mental health needs.
Health-related quality of life and its influencing factors in adult patients with localized scleroderma - a cross-sectional study
Authors: Lis-Święty Anna , Skrzypek-Salamon Alina , Ranosz-Janicka Irmina , Brzezińska-Wcisło Ligia 
Published: May 2020

Abstract
Background
Localized Scleroderma (LoS) is an autoimmune connective tissue disease that affects skin and less commonly subcutaneous tissues. The illness occurs in children and adults, and may have a serious impact on health-related quality of life (HRQoL). The goal of this study was to explore what factors might deteriorate scores on HRQoL measures in adult LoS patients.

Methods
Detailed information on the demographic and clinical features of LoS patients was collected. The HRQoL was assessed using Skindex-29 and Short form 36 (SF-36) questionnaires.

Results
Thirty three women and seven men with LoS were enrolled. Female gender negatively influenced scores for the emotion subscale of Skindex-29. Multiple-factor linear regression analysis confirmed, as with single-factor analysis, that the causes of low SF-36 physical component score (PCS) were subjective symptoms (pruritus, pain, paresthesia), musculoskeletal manifestations and older age at the time of survey, while rural area of residence negatively affected the SF-36 mental component score. Additionally, single-factor analysis showed that the SF-36 PCS was related to the LoS cutaneous assessment tool (LoSCAT) summary score.

Conclusions
Apart from a clinical presentations, sociodemographic characteristics, including older age, female gender and living conditions, may impair HRQoL of LoS patients. Further studies that will examine the role of these factors for physical and mental functioning of adults with LoS are needed.
Quality of life during chemotherapy, hormonotherapy or antiHER2 therapy of patients with advanced, metastatic breast cancer in clinical practice
Authors: Adamowicz Krzysztof , Baczkowska-Waliszewska Zuzanna 
Published: May 2020

Abstract
Introduction
Breast cancer is one of the most important health problems in the world. In recent years, this cancer has achieved a reduction in mortality, which is attributed to the introduction of mass screening and greater efficacy of post-operative treatment. Many patients with breast cancer have indications only for palliative therapy, but the impact of these methods on the quality of life of patients remains a subject of controversy. It remains unknown whether the progress in improving the quality of life in clinical trials also applies to patients treated as part of daily clinical practice. Data on the results of the impact of conducted therapies on the quality of life outside of clinical trials are scarce.

Methods
The results of palliative chemotherapy and first-line hormonotherapy in 351 patients with advanced, metastatic breast cancer treated in the period from January 2010 to December 2016 in two centres were analysed.

Results
The average age of patients was 62 ± 9.8 years; 139 patients received chemotherapy, 91 - therapy containing trastuzumab, and 121 - hormone therapy. A partial response was obtained in 111 patients (32%), stabilization in 150 (43%), and in 90 patients (26%) progression. Median survival time in the whole group of patients was 36 months. Chemotherapy compared to trastuzumab and hormonotherapy was associated with greater total toxicity (p = 0.03). There was a significant relationship between the type of therapy (hormonotherapy, chemotherapy, targeted therapy) and the general average quality of women’s life measured with the EORC-QLQ-C30 questionnaire. In addition, a statistically significant difference was found in some somatic complaints (the scale of QLQ-BR23 symptoms) depending on the type of therapy performed. The lowest intensity of complaints was reported by patients during hormonotherapy, then during targeted therapy, and the largest during chemotherapy.

Conclusions
There is no effect of chemotherapy on the overall quality of life. Hormone therapy and trastuzumab therapy improved the quality of life of the treated patients in clinical practice.