bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of angiotensin-converting enzyme in myeloid cell immune responses
Authors: Cao Duo-Yao , Saito Suguru , Veiras Luciana C. , Okwan-Duodu Derick , Bernstein Ellen A. , Giani Jorge F. , Bernstein Kenneth E. , Khan Zakir 
Published: May 2020

AbstractAngiotensin-converting enzyme (ACE), a dicarboxypeptidase, plays a major role in the regulation of blood pressure by cleaving angiotensin I into angiotensin II (Ang II), a potent vasoconstrictor. Because of its wide substrate specificity and tissue distribution, ACE affects many diverse biological processes. In inflammatory diseases, including granuloma, atherosclerosis, chronic kidney disease and bacterial infection, ACE expression gets upregulated in immune cells, especially in myeloid cells. With increasing evidences connecting ACE functions to the pathogenesis of these acquired diseases, it is suggested that ACE plays a vital role in immune functions. Recent studies with mouse models of bacterial infection and tumor suggest that ACE plays an important role in the immune responses of myeloid cells. Inhibition of ACE suppresses neutrophil immune response to bacterial infection. In contrast, ACE overexpression in myeloid cells strongly induced bacterial and tumor resistance in mice. A detailed biochemical understanding of how ACE activates myeloid cells and which ACE peptide(s) (substrate or product) mediate these effects could lead to the development of novel therapies for boosting immunity against a variety of stimuli, including bacterial infection and tumor.
Design of high-oleic tobacco (Nicotiana tabacum L.) seed oil by CRISPR-Cas9-mediated knockout of NtFAD2–2
Authors: Tian Yinshuai , Chen Kai , Li Xiao , Zheng Yunpu , Chen Fang 
Published: May 2020

Abstract
Background
Tobacco seed oil could be used as an appropriate feedstock for biodiesel production. However, the high linoleic acid content of tobacco seed oil makes it susceptible to oxidation. Altering the fatty acid profile by increasing the content of oleic acid could improve the properties of biodiesel produced from tobacco seed oil.

Results
Four FAD2 genes, NtFAD2–1a, NtFAD2–1b, NtFAD2–2a, and NtFAD2–2b, were identified in allotetraploid tobacco genome. Phylogenetic analysis of protein sequences showed that NtFAD2–1a and NtFAD2–2a originated from N. tomentosiformis, while NtFAD2–1b and NtFAD2–2b from N. sylvestris. Expression analysis revealed that NtFAD2–2a and NtFAD2–2b transcripts were more abundant in developing seeds than in other tissues, while NtFAD2–1a and NtFAD2–1b showed low transcript levels in developing seed. Phylogenic analysis showed that NtFAD2–2a and NtFAD2–2b were seed-type FAD2 genes. Heterologous expression in yeast cells demonstrated that both NtFAD2–2a and NtFAD2–2b protein could introduce a double bond at the Δ12 position of fatty acid chain. The fatty acid profile analysis of tobacco fad2–2 mutant seeds derived from CRISPR-Cas9 edited plants showed dramatic increase of oleic acid content from 11% to over 79%, whereas linoleic acid decreased from 72 to 7%. In addition, the fatty acid composition of leaf was not affected in fad2–2 mutant plants.

Conclusion
Our data showed that knockout of seed-type FAD2 genes in tobacco could significantly increase the oleic acid content in seed oil. This research suggests that CRISPR-Cas9 system offers a rapid and highly efficient method in the tobacco seed lipid engineering programs.
Interleukin-6 is associated with acute concussion in military combat personnel
Authors: Edwards Katie A. , Gill Jessica M. , Pattinson Cassandra L. , Lai Chen , Brière Misha , Rogers Nicholas J. , Milhorn Denise , Elliot Jonathan , Carr Walter 
Published: May 2020

Abstract
Background
Concussion is the most common type of TBI, yet reliable objective measures related to these injuries and associated recovery processes remain elusive, especially in military personnel. The purpose of this study was to characterize the relationship between cytokines and recovery from acute brain injury in active duty service members. Inflammatory cytokines (IL-6, IL-10, and TNFα) were measured acutely in blood samples within 8 h following a medically diagnosed concussion and then 24 h later.

Methods
Participants (n = 94) were categorized into two groups: 1) military personnel who sustained provider-diagnosed concussion, without other major medical diagnosis (n = 45) and 2) healthy control participants in the same deployment environment who did not sustain concussion or other illness or injuries (n = 49). IL-6, IL-10, and TNFα concentrations were measured using an ultrasensitive single-molecule enzyme-linked immunosorbent assay. Differences in cytokine levels between concussed and healthy groups were evaluated at two time points (time point 1 ≤ 8 h after injury; time point 2 = 24 h following time point 1).

Results
At time point 1, IL-6 median (IQR) concentrations were 2.62 (3.62) in the concussed group, which was greater compared to IL-6 in the healthy control group (1.03 (0.90); U = 420.00, z = − 5.12, p < 0.001). Compared to healthy controls, the concussed group did not differ at time point 1 in IL-10 or TNFα concentrations (p’s > 0.05). At time point 2, no differences were detected between concussed and healthy controls for IL-6, IL-10, or TNFα (p’s > 0.05). The median difference between time points 1 and 2 were compared between the concussed and healthy control groups for IL-6, IL-10, and TNFα. Change in IL-6 across time was greater for the concussed group than healthy control (− 1.54 (3.12); U = 315.00, z = − 5.96, p < 0.001), with no differences between groups in the change of IL-10 or TNFα (p’s > 0.05).

Conclusion
Reported here is a significant elevation of IL-6 levels in concussed military personnel less than 8 h following injury. Future studies may examine acute and chronic neurological symptomology associated with inflammatory cytokine levels, distinguish individuals at high risk for developing neurological complications, and identify underlying biological pathways to mitigate inflammation and improve outcomes.
Efficacy of interventions for amblyopia: a systematic review and network meta-analysis
Authors: Li Yonghong , Sun Huan , Zhu Xiaojuan , Su Yana , Yu Tianqi , Wu Xinyu , Zhou Xiaoqin , Jing Li 
Published: May 2020

Abstract
Background
Many treatments are currently available for amblyopic patients; although, the comparative efficacy of these therapies is unclear. We conducted a systematic review and network meta-analysis (NMA) to establish the relative efficacy of these treatments for amblyopia.

Methods
Electronic databases (MEDLINE, EMBASE, Cochrane Library) were systematically searched from inception to Sep. 2019. Only Randomized clinical trials comparing any two or three of the following treatments were included: refractive correction (spectacles alone), patching of 2 h per day (patch 2H), patch 6H, patch 12H, patch 2H + near activities (N), patch 2H + distant activities (D), atropine (Atr) daily, Atr weekly, Atr weekly + plano lens over the sound eye (Plano), optical penalization and binocular therapy. The reviewers independently extracted the data according to the PRISMA guidelines; assessed study quality by Cochrane risk-of-bias tool for randomized trials. The primary outcome measure was the change in best-corrected visual acuity (BCVA) expressed as log MAR lines. Direct comparisons and a Bayesian meta-analysis were performed to synthesize data.

Results
Twenty-three studies with 3279 patients were included. In the network meta-analysis, optical penalization was the least effective of all the treatments for the change of visual acuity, spectacles (mean difference [MD], 2.9 Log MAR lines; 95% credibility interval [CrI], 1.8–4.0), patch 2H (MD, 3.3; 95% CrI, 2.3–4.3), patch 6H (MD, 3.6; 95% CrI, 2.6–4.6), patch 12H (MD, 3.4; 95% CrI, 2.3–4.5), patch 2H + N (MD, 3.7; 95% CrI, 2.5–5.0), patch 2H + D (MD, 3.5; 95% CrI, 2.1–5.0), Atr daily (MD, 3.2; 95% CrI, 2.2–4.3), Atr weekly (MD, 3.2; 95% CrI, 2.2–4.3), Atr weekly + Plano (MD, 3.7; 95% CrI, 2.7–4.7), binocular therapy (MD, 3.1; 95% CrI, 2.0–4.2). The patch 6H and patch 2H + N were better than spectacles ([MD, 0.73; 95% Crl, 0.10–1.40]; [MD, 0.84; 95% CrI, 0.19–1.50]).

Conclusions
The NMA indicated that the efficacy of the most of the examined treatment modalities for amblyopia were comparable, with no significant difference. Further high quality randomized controlled trials are required to determine their efficacy and acceptability.

Systematic review registration
CRD42019119843.
Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW
Authors: Weber Michel , Dominguez Marcel , Coscas Florence , Faure Céline , Baillif Stéphanie , Kodjikian Laurent , Cohen Salomon-Yves 
Published: May 2020

Abstract
Background
To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection.

Methods
RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen.

Results
The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (− 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%).

Conclusions
In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen.

Trial registration
www.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.
Exploring assessor cognition as a source of score variability in a performance assessment of practice-based competencies
Authors: Roduta Roberts Mary , Cook Megan , Chao Iris C. I. 
Published: May 2020

Abstract
Background
A common feature of performance assessments is the use of human assessors to render judgements on student performance. From a measurement perspective, variability among assessors when assessing students may be viewed as a concern because it negatively impacts score reliability and validity. However, from a contextual perspective, variability among assessors is considered both meaningful and expected. A qualitative examination of assessor cognition when assessing student performance can assist in exploring what components are amenable to improvement through enhanced rater training, and the extent of variability when viewing assessors as contributing their individual expertise. Therefore, the purpose of this study was to explore assessor cognition as a source of score variability in a performance assessment of practice-based competencies.

Method
A mixed-method sequential explanatory study design was used where findings from the qualitative strand assisted in the interpretation of results from the quantitative strand. Scores from one objective structured clinical examination (OSCE) were obtained for 95 occupational therapy students. Two Generalizability studies were conducted to examine the relative contribution of assessors as a source of score variability and to estimate the reliability of domain and holistic scores. Think-aloud interviews were conducted with eight participants assessing a subset of student performances from the OSCE in which they participated. Findings from the analysis of think-aloud data and consideration of assessors’ background characteristics were used to assist in the interpretation of variance component estimates involving assessors, and score reliability.

Results
Results from two generalizability analyses indicated the highest-order interaction-error term involving assessors accounted for the second-highest proportion of variance, after student variation. Score reliability was higher in the holistic vs. analytic scoring framework. Verbal analysis of assessors' think-aloud interviews provided evidential support for the quantitative results.

Conclusions
This study provides insight into the nature and extent of assessor variability during a performance assessment of practice-based competencies. Study findings are interpretable from the measurement and contextual perspectives on assessor cognition. An integrated understanding is important to elucidate the meaning underlying the numerical score because the defensibility of inferences made about students’ proficiencies rely on score quality, which in turn relies on expert judgements.
Anomalous AMPK-regulated angiotensin AT1R expression and SIRT1-mediated mitochondrial biogenesis at RVLM in hypertension programming of offspring to maternal high fructose exposure
Authors: Chao Yung-Mei , Wu Kay L. H. , Tsai Pei-Chia , Tain You-Lin , Leu Steve , Lee Wei-Chia , Chan Julie Y. H. 
Published: May 2020

AbstractBackgroundTissue oxidative stress, sympathetic activation and nutrient sensing signals are closely related to adult hypertension of fetal origin, although their interactions in hypertension programming remain unclear. Based on a maternal high-fructose diet (HFD) model of programmed hypertension, we tested the hypothesis that dysfunction of AMP-activated protein kinase (AMPK)-regulated angiotensin type 1 receptor (AT1R) expression and sirtuin1 (SIRT1)-dependent mitochondrial biogenesis contribute to tissue oxidative stress and sympathoexcitation in programmed hypertension of young offspring.MethodsPregnant female rats were randomly assigned to receive normal diet (ND) or HFD (60% fructose) chow during pregnancy and lactation. Both ND and HFD offspring returned to ND chow after weaning, and blood pressure (BP) was monitored from age 6 to 12 weeks. At age of 8 weeks, ND and HFD offspring received oral administration of simvastatin or metformin; or brain microinfusion of losartan. BP was monitored under conscious condition by the tail-cuff method. Nutrient sensing molecules, AT1R, subunits of NADPH oxidase, mitochondrial biogenesis markers in rostral ventrolateral medulla (RVLM) were measured by Western blot analyses. RVLM oxidative stress was measured by fluorescent probe dihydroethidium and lipid peroxidation by malondialdehyde assay. Mitochondrial DNA copy number was determined by quantitative real-time polymerase chain reaction.ResultsIncreased systolic BP, plasma norepinephrine level and sympathetic vasomotor activity were exhibited by young HFD offspring. Reactive oxygen species (ROS) level was also elevated in RVLM where sympathetic premotor neurons reside, alongside augmented protein expressions of AT1R and pg91phoxsubunit of NADPH oxidase, decrease in superoxide dismutase 2; and suppression of transcription factors for mitochondrial biogenesis, peroxisome proliferator-activated receptor γ co-activator α (PGC-1α) and mitochondrial transcription factor A (TFAM). Maternal HFD also attenuated AMPK phosphorylation and protein expression of SIRT1 in RVLM of young offspring. Oral administration of a HMG-CoA reductase inhibitor, simvastatin, or an AMPK activator, metformin, to young HFD offspring reversed maternal HFD-programmed increase in AT1R and decreases in SIRT1, PGC-1α and TFAM; alleviated ROS production in RVLM, and attenuated sympathoexcitation and hypertension.ConclusionDysfunction of AMPK-regulated AT1R expression and SIRT1-mediated mitochondrial biogenesis may contribute to tissue oxidative stress in RVLM, which in turn primes increases of sympathetic vasomotor activity and BP in young offspring programmed by excessive maternal fructose consumption.
Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes
Authors: Togun Toyin , Kampmann Beate , Stoker Neil Graham , Lipman Marc 
Published: May 2020

AbstractThe COVID-19 pandemic has currently overtaken every other health issue throughout the world. There are numerous ways in which this will impact existing public health issues. Here we reflect on the interactions between COVID-19 and tuberculosis (TB), which still ranks as the leading cause of death from a single infectious disease globally. There may be grave consequences for existing and undiagnosed TB patients globally, particularly in low and middle income countries (LMICs) where TB is endemic and health services poorly equipped. TB control programmes will be strained due to diversion of resources, and an inevitable loss of health system focus, such that some activities cannot or will not be prioritised. This is likely to lead to a reduction in quality of TB care and worse outcomes. Further, TB patients often have underlying co-morbidities and lung damage that may make them prone to more severe COVID-19. The symptoms of TB and COVID-19 can be similar, with for example cough and fever. Not only can this create diagnostic confusion, but it could worsen the stigmatization of TB patients especially in LMICs, given the fear of COVID-19. Children with TB are a vulnerable group especially likely to suffer as part of the “collateral damage”. There will be a confounding of symptoms and epidemiological data through co-infection, as happens already with TB–HIV, and this will require unpicking. Lessons for COVID-19 could be learned from the vast experience of running global TB control programmes, while the astonishingly rapid and relatively well co-ordinated response to COVID-19 demonstrates how existing programmes could be significantly improved.
ApoE and apoC-III-defined HDL subtypes: a descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity
Authors: Amaya-Montoya Mateo , Pinzón-Cortés Jairo A. , Silva-Bermúdez Lina S. , Ruiz-Manco Daniel , Pérez-Matos Maria C. , Jiménez-Mora Mario A. , Mendivil Carlos O. 
Published: May 2020

Abstract
Background
The functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans.

Methods
Eighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E + C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E + C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using non-denaturing electrophoresis and anti-apoA-I western blotting.

Results
HDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6% of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8, 12.2 and 8.37% of plasma LCAT respectively for E + C-, E-C+ and E + C+). LCAT mass was lower in E + C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r = − 0.55, P = 0.017) and E-C- alpha 1 HDL (r = − 0.49, P = 0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r = 0.52, P = 0.025).

Conclusions
The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.
The lack of selection criteria for surgery in patients with non-colorectal non-neuroendocrine liver metastases
Authors: Bohlok Ali , Lucidi Valerio , Bouazza Fikri , Daher Ali , Germanova Desislava , Van Laethem Jean Luc , Hendlisz Alain , Donckier Vincent 
Published: May 2020

AbstractBackgroundThe benefit of surgery in patients with non-colorectal non-neuroendocrine liver metastases (NCRNNELM) remains controversial. At the population level, several statistical prognostic factors and scores have been proposed but inconsistently verified. At the patient level, no selection criteria have been demonstrated to guide individual therapeutic decision making. We aimed to evaluate potential individual selection criteria to predict the benefit of surgery in patients undergoing treatment for NCRNNELM.MethodsData for 114 patients undergoing surgery for NCRNNELM were reviewed. In this population, we identified an early relapse group (ER), defined as patients with unresectable recurrence < 1 year postoperatively who did not benefit from surgery (N= 28), and a long-term survival group (LTS), defined as patients who were recurrence-free ≥ 5 years postoperatively and benefited from surgery (N= 20). Clinicopathologic parameters, the Association Française de Chirurgie (AFC) score, and a modified 4-point Clinical Risk Score (mCRS) (excluding CEA level) were analyzed and compared between LTS and ER groups.ResultsThe majority of patients were female and a majority had an ASA score ≤ 2 at the time of liver surgery. The median age was 55 years. Almost half of the patients (46%) presented with a single-liver metastasis. Intermediate- and low-risk AFC scores represented 40% and 60% of the population, respectively. Five- and 10-year overall survival (OS) and disease-free survival (DFS) rates were 56% and 27%, and 30% and 12%, respectively. Negative prognostic factors were the size of liver metastases > 50 mm and delay between primary and NCRNNELM <24 months for OS and DFS, respectively. AFC score was not prognostic while high-risk mCRS (scores 3–4) was predictive for the poorer OS. The clinicopathologic parameters were similar in the ER and LTS groups, except the presence of N+ primary tumor, and the size of liver metastases was significantly higher in the ER group.ConclusionIn patients with resectable NCRNNELM, no predictive factors or scores were found to accurately preoperatively differentiate individual cases in whom surgery would be futile from those in whom surgery could be associated with a significant oncological benefit.