bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells
Authors: Sommariva Sara , Caviglia Giacomo , Ravera Silvia , Frassoni Francesco , Benvenuto Federico , Tortolina Lorenzo , Castagnino Nicoletta , Parodi Silvio , Piana Michele 
Published: May 2021

Abstract
Colorectal cancer (CRC) is one of the most deadly and commonly diagnosed tumors worldwide. Several genes are involved in its development and progression. The most frequent mutations concern APC, KRAS, SMAD4, and TP53 genes, suggesting that CRC relies on the concomitant alteration of the related pathways. However, with classic molecular approaches, it is not easy to simultaneously analyze the interconnections between these pathways. To overcome this limitation, recently these pathways have been included in a huge chemical reaction network (CRN) describing how information sensed from the environment by growth factors is processed by healthy colorectal cells. Starting from this CRN, we propose a computational model which simulates the effects induced by single or multiple concurrent mutations on the global signaling network. The model has been tested in three scenarios. First, we have quantified the changes induced on the concentration of the proteins of the network by a mutation in APC, KRAS, SMAD4, or TP53. Second, we have computed the changes in the concentration of p53 induced by up to two concurrent mutations affecting proteins upstreams in the network. Third, we have considered a mutated cell affected by a gain of function of KRAS, and we have simulated the action of Dabrafenib, showing that the proposed model can be used to determine the most effective amount of drug to be delivered to the cell. In general, the proposed approach displays several advantages, in that it allows to quantify the alteration in the concentration of the proteins resulting from a single or multiple given mutations. Moreover, simulations of the global signaling network of CRC may be used to identify new therapeutic targets, or to disclose unexpected interactions between the involved pathways.
Associations of Maternal Complaints to Levator Ani Muscle Trauma Within 9 Months After Vaginal Birth – A Prospective Observational Cohort Study
Authors: Kimmich Nina , Birri Jana , Richter Anne , Zimmermann Roland , Kreft Martina 
Published: May 2021

Abstract
BackgroundPelvic floor trauma in form of partial or complete avulsions of the levator ani muscle (LAM) affects 6-42% of women after vaginal birth and can cause tremendous long-term morbidity. Many studies assessed morphological pelvic floor trauma after childbirth, but lacked to evaluate women`s associated short-term complaints. A proper assessment of trauma and subjective complaints after birth could help to assess possible associations between them and their relevance to women`s daily life. Therefore, we aimed to assess women`s complaints within the first months after birth in association to their LAM trauma.MethodsBetween 3/2017 and 4/2019, we prospectively evaluated vaginal births of 212 primiparous women with singletons in vertex presentation ≥ 36+0 gestational weeks for levator ani muscle (LAM) trauma by translabial ultrasound, for pelvic organ prolapse by clinical examination, and for urogynecological complaints using questionnaires 1-4 days (P1), 6-10 weeks (P2) and 6-9 months (P3) after birth. Women`s complaints were evaluated for P1-P3 according to their LAM trauma state.ResultsAt P1, 67% of women showed an intact LAM, whereas 14.6% presented a hematoma, 6.6% a partial avulsion (PAV) and 11.8% a complete avulsion (CAV). At P2, 75.9% showed an intact LAM, 9.9% a PAV and 14.2% a CAV. At P3, 72.9% of women with a LAM trauma in P1 and/or P2 were assessed, with 21.6% being intact and 39.2% having a PAV and CAV respectively. Obstetrical and baseline characteristics differed slightly between the groups. When comparing the time before and during pregnancy with the time after childbirth, birth itself affected women`s complaints in all LAM state groups, but the presence of a LAM trauma, especially a CAV, had more negative effects. ConclusionsVaginal birth changes the anatomical structure of the maternal birth canal and genital tract, and it alters women`s perceptions and body function. In our study, LAM trauma did not change these effects tremendously within the first months additionally. Therefore, other maternal, fetal and obstetrical factors need consideration for the explanation of maternal complaints, in addition to long-term effects of trauma and dysfunction of the LAM and other birth canal structures.
Understanding Nutrient Imbalances in Maize (Zea mays L.) using the Diagnosis and Recommendation Integrated System (DRIS) Approach in the Maize Belt of Nigeria
Authors: Aliyu Kamaluddin T. , Huising Jeroen , Kamara Alpha Y. , Jibrin Jibrin M. , Mohammed Ibrahim B. , Nziguheba Generose , Adam Adam M. , Vanlauwe Bernard 
Published: May 2021

Abstract
Low nutrient use efficiency in maize as a result of imbalanced nutrition has been reported to drastically reduce yield. We implemented, a nutrient omission experiment to assess the effect of nutrient application on maize yield and nutritional balance. Maize ear leaves were analyzed for nutrients, to identify nutrient balance status using the Diagnostic and Recommendation Integrated System (DRIS) approach. Results indicated that omission of N or P resulted in highly imbalanced DRIS indices respectively, and significantly lower grain yield. A strong inverse relationship between K ear leaf content with DRIS index suggests that K application negatively increases K imbalance in many situations. Imbalances of Mg, Ca and Cu were more associated with higher yielding treatments. A Which-Won-Where result show that nutrient imbalances in the diagnosis were systematically frequent when N was omitted. All the diagnosed nutrients were imbalanced even under the highest yielding NPKZn treatment; indicating further opportunity for yield increase with more balanced nutrition. Balanced nutrition of maize in the maize belt of Nigeria should target application of varying amounts of N, P, K, Mg, S and Zn, depending on the soil condition. But because of complexities of nutrient interactions during uptake, it is hardly possible to realize a balanced nutrition. However, differentiating the application of antagonistic nutrients into foliar or soil-based methods is recommended for a more balanced maize nutrition.
Anomalies of the Aortic Arch in Dogs: Evaluation with the use of Multidetector Computed Tomography and Proposal of an advanced Classification Scheme
Authors: Schorn Christiane , Hildebrandt Nicolai , Schaub Sebastian 
Published: May 2021

Abstract
Background: Congenital anomalies of the aortic arch are important to recognize as they may be associated with vascular rings. The most common vascular ring anomaly in dogs is persistent right aortic arch. However, published data of the distribution and percentage of the different types of vascular rings and other aortic arch anomalies are lacking. The objective of this retrospective descriptive study was to characterize the amount and types of aortic arch anomalies that can be detected in thoracic computed tomography (CT) examination in dogs. Results: Dogs that underwent thoracic CT between 2008 and 2020 were included. A total of 213 CT studies were sampled; 21 dogs (21/213, 9.9%) showed a right aortic arch, and the following additional findings were detected: aberrant left subclavian artery (17/21, 76.2%) branching from the PDA (1/21, 4.8%), left-sided brachiocephalic trunk (3/21, 14.3%), bicarotid trunk (17/21, 81.0%), double aortic arch (1/21, 4.8%). No dog presented right aortic arch without further anomalies. Also, 192 dogs (192/213, 90.1%) showed left aortic arch. The following additional abnormalities were obtained: aberrant right subclavian artery (3/192, 1.6%) without clinical signs of vascular ring, aberrant vessel branching from the aorta into the left caudal lung lobe (2/192, 1.0%), focal dilataion of the left or right subclavian artery (2/192, 1.0%), bicarotid trunk (1/192, 0.5%). Conclusion: The current study indicates that aberrant left subclavian artery is the most common additional finding in dogs with persistent right aortic arch and that left-sided brachiocephalic trunk can occur in dogs, which was previously unpublished. Aberrant right subclavian artery can be an incidental CT finding without clinical relevance.
Predictors of the Worry About Cancer Recurrence Among Women With Breast Cancer
Authors: Safdari-Molan Masoumeh , Mehrabi Esmat , Nourizadeh Roghaiyeh , Hakimi Sevil , Nikkhesal Neda 
Published: May 2021

Abstract
Introduction: Worry about cancer recurrence is identified as the most common psychological burdens experienced by cancer patients and survivors. The present study aimed to determine the predictors of worry about cancer recurrence among women with breast cancer. Materials and methods: This cross-sectional study was conducted on 166 women with breast cancer undergoing chemotherapy and radiotherapy, who referred to private and public oncology centers in Tabriz, Iran using the convenience sampling method. Data collection tools were demographic and disease characteristics questionnaire, cancer worry scale, social support questionnaire, brief illness perception questionnaire, international physical activity questionnaire-short form, and The EORTC-in-patsat32. The data were analyzed using SPSS 25 software. Pearson correlation coefficient, independent t-test, ANOVA, and multivariate linear regression were used.Results: In the present study, the mean (standard deviation) of score of worry about cancer recurrence was 17.41 (7.88) from the range of 8-32. The results revealed that the type of surgery, illness perception, satisfaction with care, and place of treatment were the most important predictors of worry about cancer recurrence, which explained 44.3% of the variance.Conclusion: The enhancement of satisfaction with care and training coping strategies among individuals with high perceived severity of the illness contribute to the reduction of worry about cancer recurrence and adaptation to breast cancer.
Audio-visual Stimulation for Visual Compensatory Functions in Stroke Survivors With Visual Field Defect; a Systematic Review
Authors: Alwashmi Kholoud , Meyer Georg , Rowe Fiona J 
Published: May 2021

Abstract
Background: Hemianopia is a complete or partial blindness in the visual fields of both eyes, commonly caused by cerebral infarction. It has been hypothesized that systematic audio-visual (AV) stimulation of the blind hemifield can improve accuracy and search times in visual exploration, probably due to the stimulation of bimodal representations in the Superior Colliculus (SC), an important multisensory structure involved in both the initiation and execution of saccades. The review aimed to assess evidence for the effectiveness of AV stimulation as a rehabilitation strategy for stroke survivors with hemianopia in adult- and childhood.Methods: This review is registered with PROSPERO. A narrative synthesis of the findings is presented to highlight how AV rehabilitation impacts on hemianopia patients including visual oculomotor function, functional ability in activities of daily living, hemianopic dyslexia, visual scanning and searching tasks, maintaining of functional ability post training and the effect on brain multisensory integration by using neuroimaging.Results: Sixteen studies were included; fourteen articles (188 participants) and two literature reviews. Results were grouped into AV training of hemianopia in adults and in children, and then further grouped according to the AV task-type: tasks measuring the training effects by comparing visual stimulation training to audio-visual training, localization abilities in HH, and AV integration in patients with HH.Conclusion: The review findings support the concept that compensatory audio-visual training can be useful as rehabilitation method for stroke survivors with hemianopia. Systematic AV training may improve the processing of visual information by recruiting subcortical pathways, and because most of the patients with visual cortex damage have an intact SC, it might be useful to use the bimodal AV training to activate retinotectal functions. Nevertheless, the underlying mechanisms supporting the reported positive effects are not currently understood. Systematic functional and/or structural imaging studies may help in understanding the underlying mechanism and inform the design of optimal training paradigms.Systematic review registration: This review is registered with PROSPERO by the correspondence author (CRD42020197348).
Standardized Assessment of Simulation Based ECMO Educational Courses: A Pilot Study
Authors: Said Ahmed S , Cooley Elaine , Diaz Rodrigo , Moore Elizabeth A , Shekar Kiran , Beaty Christopher , Maul Timothy M , Kollengode Ramanathan , Zakhary Bishoy 
Published: May 2021

Abstract
Background: The Extracorporeal Life Support Organization (ELSO) education taskforce (ELSOed) recently identified seven extracorporeal membrane oxygenation (ECMO) educational domains that would benefit from international collaborative efforts among which standardized assessments of ECMO courses was prioritized. We aimed to develop a standardized online assessment tool to evaluate the effectiveness of a comprehensive didactic and simulation-based ECMO course on participants’ gain in confidence, knowledge, and simulation-based skills.Methods: We performed a prospective multicenter observational study of five US adult ECMO courses. Standardized online assessment forms were developed and administered before and after courses, covering demographics, self-assessment regarding ECMO management, and knowledge exam (15 simple-recall multiple choice questions), while psychomotor skill assessment was performed during the course (time to complete pre-specified critical actions during simulation scenarios). Self-assessment covered cognitive, behavioral, and technical aspects of ECMO care.Results: Out of 211 participants, 107 completed both pre- and post-course forms (97 completed both pre and post-course knowledge forms). Physician-intensivists were the largest group (53%) and the majority practiced at academic hospitals (51%) and had less than 1-year of ECMO experience (50%). Post-course, participants reported significant increases in confidence across all domains (cognitive, technical, and behavioral; p<0.0001 CI:1.2-1.5, p<0.0001 CI:2.2-2.6, and p=0.002 CI:1.7-2.1, respectively) as well as an increase in knowledge scores (p<0.001, CI: 1.4-2.5). These findings were consistent for all specialties and prior ECMO experience. There were also significant reductions in the times to critical actions in 3 of the 4 scored simulation scenarios.Conclusions: We successfully developed and tested a comprehensive standardized ECMO course assessment tool, demonstrating participants’ self-reported benefit as well as improvement in both knowledge and psychomotor skill acquisition . Standardized course evaluation is feasible and potentially provides important information to improve ECMO courses. Future steps include national implementation, addition of questions targeting clinical decision making to further assess knowledge gain, and multi-language translation for implementation at international courses.
Non-invasive Estimation of Pulsatile and Static Intracranial Pressure by Optical Coherence Tomography
Authors: Jacobsen Henrik Holvin , Jørstad Øystein Kalsnes , Moe Morten C. , Petrovski Goran , Pripp Are Hugo , Sandell Tiril , Eide Per Kristian 
Published: May 2021

Abstract
This study examined whether optical coherence tomography (OCT) can be used to estimate the pulsatile and static intracranial pressure (ICP) in patients with idiopathic intracranial hypertension (IIH). Continuous overnight monitoring of the pulsatile and static ICP and a single OCT examination were performed in 20 patients with IIH and in 12 reference subjects without cerebrospinal fluid disturbances. The ICP measurements were obtained using a parenchymal sensor. The pulsatile ICP was determined as the mean ICP wave amplitude (MWA) and the static ICP was determined as the mean ICP. The IIH group had increased overnight MWA and mean ICP scores, and OCT demonstrated anterior deflection of the peripapillary Bruch’s membrane angle (pBA) and increased optic nerve head height (ONHH). There was a significant positive correlation between the pBA and ONHH and the overnight MWA scores, and between mean ICP and ONHH. The pBA and the ONHH also predicted abnormal overnight MWA, but the predictive power of mean ICP was non-significant after adjusting for age and body mass index. This study suggest that the OCT parameters pBA and ONHH can predict abnormal MWA scores.
Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy
Authors: Schworm Benedikt , Luft Nikolaus , Keidel Leonie F , Kreutzer Thomas C , Herold Tina R , Priglinger Siegfried G , Siedlecki Jakob 
Published: May 2021

Abstract
BackgroundTo investigate the diagnostic value of choroidal thickness in the definition of pachychoroid neovasculopathy (PNV), especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy.MethodsTwenty-two consecutive eyes of 11 patients with uni- or bilateral PNV were analyzed. Anti-VEGF treatment was correlated with changes in choroidal thickness on enhanced depth imaging optical coherence tomography.ResultsThere were 14 eyes with PNV and 8 non-neovascular partner eyes. Mean age was 64.2 ± 4.0 (range: 60–72), total follow-up was 1.8 ± 0.4 (1–2) years. In PNV eyes, choroidal thickness at baseline was 400 ± 58 (269–485) µm. After two years and 13 anti-VEGF injections on average, a mean reduction of -39 ± 10 (-26 to -56) % to final 241 ± 52 (162–327) µm was observed (p < 0.0001). Meanwhile, choroidal thickness in the partner eyes remained stable (p > 0.13 for all comparisons). A significant correlation of choroidal thinning and anti-VEGF injection rate was observed at year one (r=-0.79 ; R2 = 0.63 ; p = 0.00073) and two (r=-0.69; R2 = 0.48 ; p = 0.019). While 85.7 % of PNV eyes exceeded a pachychoroid threshold of ≥ 350 µm at baseline, this figure dropped to 21.4 % at year one and 0 % at year two.ConclusionIn PNV, choroidal thickness significantly decreases with anti-VEGF therapy, resembling a “vanishing pachy-choroid”, and thus does not represent a valid long-term diagnostic criterium, especially when differentiating PNV from nAMD.
De Novo Biosynthesis of Glycosylated Carotenoids in Escherichia Coli
Authors: Chen Xixian , Lim Xiaohui , Bouin Aurelie , Lautier Thomas , Zhang Congqiang 
Published: May 2021

Abstract
Carotenoids have wide applications in food, feed, pharmaceutical and cosmetic industries. The fast-growing market demands highlight the importance of developing new routes for carotenoid biosynthesis. Meanwhile, a complementary need is to improve low bioavailability because of the hydrophobicity of carotenoids. One solution is glycosylation, which can substantially increase the water solubility of carotenoids, and enhance the bioavailability, photostability and biological activities as food supplements and medicines. Here, we report metabolic engineering efforts to produce glycosylated carotenoids in Escherichia coli . By fine tuning the 14 gene pathway, our strain produced up to 47.2 mg/L (~11670 ppm) of zeaxanthin glucosides, ~78% of the total carotenoids produced. In another construct with 15-gene pathway, the strain produced a mixture of carotenoid glucosides including astaxanthin and adonixanthin glucosides with a total yield of 8.1 mg/L (1774 ppm). Our work demonstrated a proof-of-concept study for the microbial biosynthesis of glycosylated carotenoids. (145 words)
Economic Evaluation of Community-based Falls Prevention Interventions: a Systematic Methodological Overview of Systematic Reviews
Authors: Kwon Joseph , Lee Yujin , Squires Hazel , Franklin Matt , Young Tracey 
Published: May 2021

Abstract
Background: Falls impose significant health and economic burdens on older people, making their prevention a priority for care decision-makers. The volume of falls prevention economic evaluations has increased, the findings from which have been synthesised by systematic reviews (SRs) with pre-specified criteria (e.g., objectives, eligibility, data extraction). Such SRs can inform commissioning and design of future evaluations, particularly decision models; however, their findings can be biased and partial dependent on their pre-specified criteria. This study aims to conduct a systematic overview (SO) to: (1) systematically identify SRs of community-based falls prevention economic evaluations; (2) describe the methodology and findings of SRs; (3) critically appraise the methodology of SRs; and (4) suggest commissioning recommendations based on SO findings. Methods: The SO followed the PRISMA guideline and the Cochrane guideline on SO, covering the period 2003-2020. Identified SRs’ aims, search strategies and results, extracted data fields, quality assessment methods and results, and commissioning and research recommendations were synthesised. The comprehensiveness of previous SRs’ data synthesis was judged against criteria drawn from expert guideline and academic literature on falls prevention/public health economic evaluation. Outcomes of general population, lifetime decision models were re-analysed to inform commissioning recommendations. The SO protocol is registered in the Prospective Register of Systematic Reviews (CRD42021234379).Results: Seven SRs were identified, which extracted 8 to 33 data fields from 44 relevant economic evaluations. Four economic evaluation methodological/reporting quality checklists were used; three SRs narratively synthesised methodological features to varying extent and focus. SRs generally did not appraise decision modelling features, including methods for characterising dynamic complexity of falls risk and intervention need. Their commissioning recommendations were based mainly on cost-per-unit ratios (e.g., incremental cost-effectiveness ratios) and neglected aggregate impact. There is model-based evidence of multifactorial and environmental interventions, home assessment and modification and Tai Chi being cost-effective but also the risk that they exacerbate social inequities of health. Conclusions: Current SRs of falls prevention economic evaluations do not holistically inform commissioning and evaluation design. Accounting for broader decisional factors including intervention reach and capacity constraints and a broader grasp of methodological nuances of economic evaluations, particularly decision models, are needed.