bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/Cas9-mediated knockout of clinically relevant alloantigenes in human primary T cells
Authors: Kamali Elahe , Rahbarizadeh Fatemeh , Hojati Zohreh , Frödin Morten 
Published: January 2021

AbstractBackgroundThe ability of CRISPR/Cas9 to mutate any desired genomic locus is being increasingly explored in the emerging area of cancer immunotherapy. In this respect, current efforts are mostly focused on the use of autologous (i.e. patient-derived) T cells. The autologous approach, however, has drawbacks in terms of manufacturing time, cost, feasibility and scalability that can affect therapeutic outcome or wider clinical application. The use of allogeneic T cells from healthy donors may overcome these limitations. For this strategy to work, the endogenous T cell receptor (TCR) needs to be knocked out in order to reduce off-tumor, graft-versus-host-disease (GvHD). Furthermore, CD52 may be knocked out in the donor T cells, since this leaves them resistant to the commonly used anti-CD52 monoclonal antibody lymphodepletion regimen aiming to suppress rejection of the infused T cells by the recipient. Despite the great prospect, genetic manipulation of human T cells remains challenging, in particular how to deliver the engineering reagents: virus-mediated delivery entails the inherent risk of altering cancer gene expression by the genomically integrated CRISPR/Cas9. This is avoided by delivery of CRISPR/Cas9 as ribonucleoproteins, which, however, are fragile and technically demanding to produce. Electroporation of CRISPR/Cas9 expression plasmids would bypass the above issues, as this approach is simple, the reagents are robust and easily produced and delivery is transient.ResultsHere, we tested knockout of either TCR or CD52 in human primary T cells, using electroporation of CRISPR/Cas9 plasmids. After validating the CRISPR/Cas9 constructs in human 293 T cells by Tracking of Indels by Decomposition (TIDE) and Indel Detection by Amplicon Analysis (IDAA) on-target genomic analysis, we evaluated their efficacy in primary T cells. Four days after electroporation with the constructs, genomic analysis revealed a knockout rate of 12–14% for the two genes, which translated into 7–8% of cells showing complete loss of surface expression of TCR and CD52 proteins, as determined by flow cytometry analysis.ConclusionOur results demonstrate that genomic knockout by electroporation of plasmids encoding CRISPR/Cas9 is technically feasible in human primary T cells, albeit at low efficiency.
Exploring nursing managers’ perceptions of nursing workforce management during the outbreak of COVID-19: a content analysis study
Authors: Poortaghi Sarieh , Shahmari Mehraban , Ghobadi Akram 
Published: January 2021

Abstract
Background
The COVID-19 pandemic is a serious threat to public health worldwide. Therefore, a coordinated global response is needed to prepare health care systems to face this unprecedented challenge. Proper human resource management can increase nurses’ productivity and quality of care. Therefore, the present study aims to explore the nursing managers’ perception of nursing workforce management during the outbreak of COVID-19.

Methods
This is a qualitative study with conventional content analysis using Granheim and Landman approach. In this study, 15 nursing managers were selected by purposeful sampling method. Data were collected using in-depth semi-structured interviews. Ethical considerations were applied to all stages of the study. In this study, MAXQDA software version 10 was used to help manage the data.

Results
66% of the participants (10/5) were female. The mean age of participants was 44 years, mean work experience of 19 years, and mean management experience of 9 years. Three categories and seven sub-categories emerged from the data analysis: 1) management of workforce recruitment (volunteer workforces, non-volunteer workforces), 2) management of workforce arrangement (flexible work schedule, rearrangement of the workforce), and 3) management of workforce retention (preventive measures, motivational measures, and psychological support).

Conclusion
Management in critical situations requires the use of flexible and situational management principles to recruit, arrange and retain workforce, and also to compensate for the lack of manpower.
Emerging interactions between diet, gastrointestinal helminth infection, and the gut microbiota in livestock
Authors: Williams Andrew R. , Myhill Laura J. , Stolzenbach Sophie , Nejsum Peter , Mejer Helena , Nielsen Dennis S. , Thamsborg Stig M. 
Published: January 2021

AbstractIncreasing evidence suggests that nutritional manipulation of the commensal gut microbiota (GM) may play a key role in maintaining animal health and production in an era of reduced antimicrobial usage. Gastrointestinal helminth infections impose a considerable burden on animal performance, and recent studies suggest that infection may substantially alter the composition and function of the GM. Here, we discuss the potential interactions between different bioactive dietary components (prebiotics, probiotics and phytonutrients) and helminth infection on the GM in livestock. A number of recent studies suggest that host diet can strongly influence the nature of the helminth-GM interaction. Nutritional manipulation of the GM may thus impact helminth infection, and conversely infection may also influence how the GM responds to dietary interventions. Moreover, a dynamic interaction exists between helminths, the GM, intestinal immune responses, and inflammation. Deciphering the mechanisms underlying the diet-GM-helminth axis will likely inform future helminth control strategies, as well as having implications for how health-promoting feed additives, such as probiotics, can play a role in sustainable animal production.
Gene expression profiling for the diagnosis of multiple primary malignant tumors
Authors: Zheng Yu , Sun Yifeng , Kuai Yue , Fu Guoxiang , An Huimin , Chen Jinyun , Chen Jinying , Zhu Jiajun , Wo Yixin , Wu Yiwang , Song Kaibin , Xu Qinghua , Wu Di , Huang Deshuang , Wang Qifeng , Pan Hongming 
Published: January 2021

Abstract
Background
The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice.

Methods
In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay.

Results
For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84–0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82–0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82–0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47–0.99) for identifying the tumor origins.

Conclusions
The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.
Hepatic safety of repeated treatment with pyronaridine‐artesunate versus artemether–lumefantrine in patients with uncomplicated malaria: a secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso
Authors: Compaoré Yves Daniel , Zongo Issaka , Somé Anyirékun F. , Barry Nouhoun , Nikiéma Frederick , Kaboré Talato N. , Ouattara Aminata , Kabré Zachari , Wermi Kadidiatou , Zongo Moussa , Yerbanga Rakiswende S. , Sagara Issaka , Djimdé Abdoulaye , Ouédraogo Jean Bosco 
Published: January 2021

AbstractBackgroundThe use of pyronaridine-artesunate (PA) has been associated with scarce transaminitis in patients. This analysis aimed to evaluate the hepatic safety profile of repeated treatment with PA versus artemether–lumefantrine (AL) in patients with consecutive uncomplicated malaria episodes in Bobo-Dioulasso, Burkina Faso.MethodsThis study analysed data from a clinical trial conducted from 2012 to 2015, in which participants with uncomplicated malaria were assigned to either PA or AL arms and followed up to 42 days. Subsequent malaria episodes within a 2-years follow up period were also treated with the same ACT initially allocated. Transaminases (AST/ALT), alkaline phosphatase (ALP), total and direct bilirubin were measured at days 0 (baseline), 3, 7, 28 and on some unscheduled days if required. The proportions of non-clinical hepatic adverse events (AEs) following first and repeated treatments with PA and AL were compared within study arms. The association of these AEs with retreatment in each arm was also determined using a logistic regression model.ResultsA total of 1379 malaria episodes were included in the intention to treat analysis with 60% of all cases occurring in the AL arm. Overall, 179 non-clinical hepatic AEs were recorded in the AL arm versus 145 in the PA arm. Elevated ALT was noted in 3.05% of treated malaria episodes, elevated AST 3.34%, elevated ALP 1.81%, and elevated total and direct bilirubin in 7.90% and 7.40% respectively. Retreated participants were less likely to experience elevated ALT and AST than first episode treated participants in both arms. One case of Hy’s law condition was recorded in a first treated participant of the PA arm. Participants from the retreatment group were 76% and 84% less likely to have elevated ALT and AST, respectively, in the AL arm and 68% less likely to present elevated ALT in the PA arm. In contrast, they were almost 2 times more likely to experience elevated total bilirubin in both arms.ConclusionsPyronaridine-artesunate and artemether–lumefantrine showed similar hepatic safety when used repeatedly in participants with uncomplicated malaria. Pyronaridine-artesunate represents therefore a suitable alternative to the current first line anti-malarial drugs in use in endemic areas.Trial registrationPan African Clinical Trials Registry. PACTR201105000286876
Dietary intake of branched-chain amino acids in relation to depression, anxiety and psychological distress
Authors: Koochakpoor Glareh , Salari-Moghaddam Asma , Keshteli Ammar Hassanzadeh , Afshar Hamid , Esmaillzadeh Ahmad , Adibi Peyman 
Published: January 2021

Abstract
Background
There is no previous study that examined the association between branched-chain amino acids (BCAAs) intake and odds of psychological disorders. The aim of this study was to investigate the association between dietary BCAAs and odds of psychological disorders including depression, anxiety, and psychological distress in a large sample of Iranian adults.

Methods
In this cross-sectional study on 3175 Iranian adults aged 18–55 years, a validated food frequency questionnaire was used to assess dietary intakes. BCAAs intake was computed by summing up the amount of valine, leucine, and isoleucine intake from all food items in the questionnaire. Psychological health was examined through the use of Iranian validated version of the Hospital Anxiety and Depression Scale (HADS). Psychological distress was assessed using General Health Questionnaire (GHQ). For depression and anxiety, scores of 8 or more on either subscale were considered as psychological disorders and scores of 0–7 were defined as “normal”. In terms of psychological distress, the score of 4 or more was defined as psychological distress.

Results
Mean age of study participants was 36.2 ± 7.8 years. Overall, 26.4% (n = 837) of study subjects had depression, 11.9% (n = 378) had anxiety and 20.9% (n = 665) were affected by psychological distress. After controlling for potential confounders, participants in the highest tertile of total BCAAs intake had lower odds of depression (OR: 0.76; 95% CI: 0.60–0.96) and anxiety (OR: 0.66; 95% CI: 0.47–0.91) compared with those in the lowest tertile. Participants in the top tertile of valine intake had a lower odds of depression (OR: 0.76; 95% CI: 0.60–0.96) and anxiety (OR: 0.65; 95% CI: 0.47–0.90) compared with those in the bottom tertile. A significant inverse association was also seen between leucine intake and depression (OR: 0.77; 95% CI: 0.61–0.98) and anxiety (OR: 0.66; 95% CI: 0.47–0.91). In addition, a significant inverse association was observed between isoleucine intake and odds of depression (OR: 0.75; 95% CI: 0.59–0.95) and anxiety (OR: 0.62; 95% CI: 0.45–0.86). There was no significant association between isoleucine intake and odds of psychological distress.

Conclusion
Evidence indicating an inverse association between dietary intake of BCAAs and odds of depression and anxiety was found. Prospective studies are required to confirm these findings.
The effects of canola and olive oils consumption compared to sunflower oil, on lipid profile and hepatic steatosis in women with polycystic ovarian syndrome: a randomized controlled trial
Authors: Yahay Maryam , Heidari Zahra , Allameh Zahra , Amani Reza 
Published: January 2021

Abstract
Background
Polycystic Ovarian Syndrome (PCOS) is one of the most common endocrinopathies and metabolic disorders in women during their reproductive years. It is often associated with dyslipidemia and other risk factors of cardiovascular diseases (CVD). This study was aimed to evaluate dietary intervention effects with canola and olive oils compared to sunflower oil on lipid profile and fatty liver severity among women with PCOS.

Method
This study was a 10-week intervention including 72 women with PCOS. Patients were randomly assigned to three groups for receiving 25 g/day canola, olive, or sunflower oils for 10 weeks. The primary and secondary outcomes were to assess changes in lipid profile and in fatty liver severity, respectively.

Result
At the end of the study, 72 patients with a mean age of 29.31 were analysed. Canola oil consumption resulted in a significant reduction in serum levels of TG (P = 0.002) and TC/HDL (P = 0.021), LDL/HDL (P = 0.047), and TG/HDL (P = 0.001) ratios, however, there was no significant reduction in lipid profile following olive oil consumption. Canola (P < 0.001) and olive oils (P = 0.005) could significantly reduce the fatty liver grade. Moreover, HOMA-IR in both canola (P < 0.001) and olive (P = 0.004) groups was significantly decreased.

Conclusion
In total, compared to olive and sunflower oils, significant improvements in lipid profile, liver function, and HOMA-IR were observed following canola oil consumption in women with PCOS.

Trial registration
IR.MUI.RESEARCH.REC.1397.315. Registered 30 JUNE 2019 - Retrospectively registered, https://www.irct.ir/trial/38684
Co-production in local government: process, codification and capacity building of new knowledge in collective reflection spaces. Workshops findings from a UK mixed methods study
Authors: van der Graaf Peter , Cheetham Mandy , Redgate Sam , Humble Clare , Adamson Ashley 
Published: January 2021

AbstractBackgroundCo-production of research evidence is valued by local government to improve effective decision-making about public services in times of austerity. However, underlying structural issues of power (so-called ‘dark shadows of co-production’) challenge this ambition with limited evidence on how to embed research use sustainably. In this paper we reflect on mechanisms for increasing co-production in local government.MethodsThis paper presents findings from a Health Foundation funded research project that explored how a culture of evidence use to improve population health could be embedded in UK local government. Five linked work packages were undertaken using mixed methods. In this paper, we report the views of UK local authority staff who participated in four workshops (n = 54), informed by a rapid literature review and an online scoping survey.ResultsWe identified five themes that facilitate public health evidence use in local government: (1) new governance arrangements to integrate national and local policies, (2) codifying research evidence through local system-wide approaches and (3) ongoing evaluation of programmes, and (4) overcoming political and cultural barriers by increasing absorptive capacity of Local Authorities to embed co-produced knowledge in their cognitive structures. This requires adaptive governance through relationship building between academic researchers and Local Authority staff and shared understanding of fragmented local policy making, which are supported by (5) collective spaces for reflection within local government.ConclusionsCreating collective spaces for reflection in between government departments allows for iterative, interactive processes of co-production with external partners that support emergence of new governance structures to socially action the co-produced knowledge in context and build capacity for sustained evidence use.
Acute systemic LPS-exposure impairs perivascular CSF distribution in mice
Authors: Manouchehrian Oscar , Ramos Marta , Bachiller Sara , Lundgaard Iben , Deierborg Tomas 
Published: January 2021

Abstract
Background
The exchange of cerebrospinal (CSF) and interstitial fluid is believed to be vital for waste clearance in the brain. The sleep-dependent glymphatic system, which is comprised of perivascular flow of CSF and is largely dependent on arterial pulsatility and astrocytic aquaporin-4 (AQP4) expression, facilitates much of this brain clearance. During the last decade, several observations have indicated that impaired glymphatic function goes hand in hand with neurodegenerative diseases. Since pathologies of the brain carry inflammatory components, we wanted to know how acute inflammation, e.g., with lipopolysaccharide (LPS) injections, would affect the glymphatic system. In this study, we aim to measure the effect of LPS on perivascular CSF distribution as a measure of glymphatic function.

Methods
Three hours after injection of LPS (1 mg/kg i.p.), C57bl/6 mice were (1) imaged for two CSF tracers, injected into cisterna magna, (2) transcardially perfused with buffer, or (3) used for physiological readouts. Tracer flow was imaged using a low magnification microscope on fixed brains, as well as using vibratome-cut slices for measuring tracer penetration in the brain. Cytokines, glial, and BBB-permeability markers were measured with ELISAs, Western blots, and immunohistochemistry. Cerebral blood flow was approximated using laser Doppler flowmetry, respiration and heart rate with a surgical monitor, and AQP4-polarization was quantified using confocal microscopy of immunolabeled brain sections.

Results
LPS-injections significantly lowered perivascular CSF tracer flow and penetration into the parenchyma. No differences in AQP4 polarization, cytokines, astroglial and BBB markers, cerebral blood flow, or respiration were detected in LPS-injected mice, although LPS did elevate cortical Iba1+ area and heart rate.

Conclusions
This study reports another physiological response after acute exposure to the bacterial endotoxin LPS, namely the statistically significant decrease in perivascular distribution of CSF. These observations may benefit our understanding of the role of systemic inflammation in brain clearance.
A comparison of methods for interpreting random forest models of genetic association in the presence of non-additive interactions
Authors: Orlenko Alena , Moore Jason H. 
Published: January 2021

Abstract
Background
Non-additive interactions among genes are frequently associated with a number of phenotypes, including known complex diseases such as Alzheimer’s, diabetes, and cardiovascular disease. Detecting interactions requires careful selection of analytical methods, and some machine learning algorithms are unable or underpowered to detect or model feature interactions that exhibit non-additivity. The Random Forest method is often employed in these efforts due to its ability to detect and model non-additive interactions. In addition, Random Forest has the built-in ability to estimate feature importance scores, a characteristic that allows the model to be interpreted with the order and effect size of the feature association with the outcome. This characteristic is very important for epidemiological and clinical studies where results of predictive modeling could be used to define the future direction of the research efforts. An alternative way to interpret the model is with a permutation feature importance metric which employs a permutation approach to calculate a feature contribution coefficient in units of the decrease in the model’s performance and with the Shapely additive explanations which employ cooperative game theory approach. Currently, it is unclear which Random Forest feature importance metric provides a superior estimation of the true informative contribution of features in genetic association analysis.

Results
To address this issue, and to improve interpretability of Random Forest predictions, we compared different methods for feature importance estimation in real and simulated datasets with non-additive interactions. As a result, we detected a discrepancy between the metrics for the real-world datasets and further established that the permutation feature importance metric provides more precise feature importance rank estimation for the simulated datasets with non-additive interactions.

Conclusions
By analyzing both real and simulated data, we established that the permutation feature importance metric provides more precise feature importance rank estimation in the presence of non-additive interactions.