Miracle-dz/UniFAR-FTUs huggingface dataset:
Opening Canada’s North: A Study of Trade Costs in the Territories

Challenged by remote locations, small populations, rugged terrain and (at times) difficult climate conditions, Canada's territories rely heavily on imported goods to maintain their standards of living. At the same time, industries in the territories are highly reliant on access to export markets – especially the large and growing resource sectors of the region. But these trade flows face significant costs that improved infrastructure may help mitigate. A northern transportation corridor could help, and has recently gained prominence following recent reports and hearings by the Senate of Canada. The potential gains are large. This paper estimates trade costs in Canada's North. We find policy-relevant trade costs (those trade costs that policy changes may help lower) are substantial. The regulatory differences, time delays and lower infrastructure quality that inhibit trade add between 20 to 30 per cent to the cost of a delivered good for Yukon and Northwest Territories and over 60 per cent for Nunavut. Infrastructure may be a large cause of higher trade costs. We find that distance-related costs are 45 per cent higher per kilometre for trade with a territory than for trade between two provinces. The region’s economy, productivity, income and investment are significantly lower as a result. Using a detailed model of the Canadian economy, we find that lowering these barriers – such as through improving northern transportation infrastructure – could add up to $6.5 billion to Canada’s GDP, with most of that gain occurring in the territories. For the Yukon, Nunavut and Northwest Territories the gains equal about $40,000 per person, which is a 50 per cent increase in productivity. The Senate’s advocacy for reducing trade barriers is encouraging and the federal government broadly supports knocking down these barriers. It is time for all three levels of government to work together to create policies on, and funding for, improved infrastructure in Canada’s North and near-North.
Histone acetylation recruits the SWR1 complex to regulate active DNA demethylation in Arabidopsis

Significance Transgenes and some endogenous genes are protected from silencing by active DNA demethylation. How the demethylase ROS1 targets these specific genomic regions is poorly understood. Here, we show that H2A.Z and components of the conserved SWR1 complex are required for antisilencing. We found that ROS1 is recruited to some of its target regions by H2A.Z deposited by the SWR1 complex. Two bromodomain-containing proteins, AtMBD9 and NPX1, are critical for the recruitment of SWR1 complex to chromatin through recognition of histone acetylation marks created by the increased DNA methylation (IDM) complex, which is known to have a regulatory role in active DNA demethylation. Thus, we have identified a complete regulatory pathway initiated by the IDM complex in active DNA demethylation in Arabidopsis. Active DNA demethylation is critical for controlling the DNA methylomes in plants and mammals. However, little is known about how DNA demethylases are recruited to target loci, and the involvement of chromatin marks in this process. Here, we identify 2 components of the SWR1 chromatin-remodeling complex, PIE1 and ARP6, as required for ROS1-mediated DNA demethylation, and discover 2 SWR1-associated bromodomain-containing proteins, AtMBD9 and nuclear protein X1 (NPX1). AtMBD9 and NPX1 recognize histone acetylation marks established by increased DNA methylation 1 (IDM1), a known regulator of DNA demethylation, redundantly facilitating H2A.Z deposition at IDM1 target loci. We show that at some genomic regions, H2A.Z and DNA methylation marks coexist, and H2A.Z physically interacts with ROS1 to regulate DNA demethylation and antisilencing. Our results unveil a mechanism through which DNA demethylases can be recruited to specific target loci exhibiting particular histone marks, providing a conceptual framework to understand how chromatin marks regulate DNA demethylation.
Towards clinical utility of polygenic risk scores.

Prediction of disease risk is an essential part of preventative medicine, often guiding clinical management. Risk prediction typically includes risk factors such as age, sex, family history of disease, and lifestyle (e.g. smoking status); however, in recent years there has been increasing interest to include genomic information into risk models. Polygenic risk scores (PRS) aggregate the effects of many genetic variants across the human genome into a single score, and have recently been shown to have predictive value for multiple common diseases. In this review, we summarise the potential use cases for seven common diseases (breast cancer, prostate cancer, coronary artery disease, obesity, type 1 diabetes, type 2 diabetes, Alzheimer's disease) where PRS has or could have clinical utility. PRS analysis for these diseases frequently revolved around (i) risk prediction performance of a PRS alone and in combination with other non-genetic risk factors, (ii) estimation of lifetime risk trajectories, (iii) the independent information of PRS and family history of disease or monogenic mutations, and (iv) estimation of the value of adding a PRS to specific clinical risk prediction scenarios. We summarise open questions regarding PRS usability, ancestry bias, and transferability, emphasising the need for the next wave of studies to focus on the implementation and health-economic value of PRS testing. In conclusion, it is becoming clear that PRS have value in disease risk prediction and there are multiple areas where this may have clinical utility.
The Influence of Astaxanthin on the Proliferation of Adipose-derived Mesenchymal Stem Cells in Gelatin-Methacryloyl (GelMA) Hydrogels

Recently, astaxanthin, a red lipophilic pigment belonging to the xanthophyllic family of carotenoids, has shown the feasibility of its uses in tissue engineering and regenerative medicine, due to its excellent antioxidant activities and its abilities to enhance the self-renewal potency of stem cells. In this study, we demonstrate the influence of astaxanthin on the proliferation of adipose-derived mesenchymal stem cells in tissue-engineered constructs. The tissue engineered scaffolds were fabricated using photopolymerizable gelatin methacryloyl (GelMA) with different concentrations of astaxanthin. The effects of astaxanthin on cellular proliferation in two-dimensional environments were assessed using alamar blue assay and reverse transcription polymerase chain reaction (RT-PCR). Then, rheological properties, chemical structures and the water absorption of the fabricated astaxanthin-incorporated GelMA hydrogels were characterized using NMR analysis, rheological analysis and a swelling ratio test. Finally, the influence in three-dimensional environments of astaxanthin-incorporated GelMA hydrogels on the proliferative potentials of adipose-derived stem cells was assessed using alamar blue assay and the confocal imaging with Live/dead staining. The experimental results of the study indicate that an addition of astaxanthin promises to induce stem cell potency via proliferation, and that it can be a useful tool for a three-dimensional culture system and various tissue engineering applications.
Sensitivity of muscle and intervertebral disc force computations to variations in muscle attachment sites

Abstract The current paper aims at assessing the sensitivity of muscle and intervertebral disc force computations against potential errors in modeling muscle attachment sites. We perturbed each attachment location in a complete and coherent musculoskeletal model of the human spine and quantified the changes in muscle and disc forces during standing upright, flexion, lateral bending, and axial rotation of the trunk. Although the majority of the muscles caused minor changes (less than 5%) in the disc forces, certain muscle groups, for example, quadratus lumborum, altered the shear and compressive forces as high as 353% and 17%, respectively. Furthermore, percent changes were higher in the shear forces than in the compressive forces. Our analyses identified certain muscles in the rib cage (intercostales interni and intercostales externi) and lumbar spine (quadratus lumborum and longissimus thoracis) as being more influential for computing muscle and disc forces. Furthermore, the disc forces at the L4/L5 joint were the most sensitive against muscle attachment sites, followed by T6/T7 and T12/L1 joints. Presented findings suggest that modeling muscle attachment sites based on solely anatomical illustrations might lead to erroneous evaluation of internal forces and promote using anatomical datasets where these locations were accurately measured. When developing a personalized model of the spine, certain care should also be paid especially for the muscles indicated in this work.
Productivity and Community Composition of Low Biomass/High Silica Precipitation Hot Springs: A Possible Window to Earth’s Early Biosphere?

Terrestrial hot springs have provided a niche space for microbial communities throughout much of Earth’s history, and evidence for hydrothermal deposits on the Martian surface suggest this could have also been the case for the red planet. Prior to the evolution of photosynthesis, life in hot springs on early Earth would have been supported though chemoautotrophy. Today, hot spring geochemical and physical parameters can preclude the occurrence of oxygenic phototrophs, providing an opportunity to characterize the geochemical and microbial components. In the absence of the photo-oxidation of water, chemoautotrophy in these hot springs (and throughout Earth’s history) relies on the delivery of exogenous electron acceptors and donors such as H2, H2S, and Fe2+. Thus, systems fueled by chemoautotrophy are likely energy substrate-limited and support low biomass communities compared to those where oxygenic phototrophs are prevalent. Low biomass silica-precipitating systems have implications for preservation, especially over geologic time. Here, we examine and compare the productivity and composition of low biomass chemoautotrophic versus photoautotrophic communities in silica-saturated hot springs. Our results indicate low biomass chemoautotrophic microbial communities in Yellowstone National Park are supported primarily by sulfur redox reactions and, while similar in total biomass, show higher diversity in anoxygenic phototrophic communities compared to chemoautotrophs. Our data suggest productivity in Archean terrestrial hot springs may be directly linked to redox substrate availability, and there may be high potential for geochemical and physical biosignature preservation from these communities.
FHR4‐based immunoconjugates direct complement‐dependent cytotoxicity and phagocytosis towards HER2‐positive cancer cells

Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b‐binding protein C‐terminal‐α‐/β‐chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent‐positive regulator of the AP, the human factor H‐related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VHH targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab‐recognising epitopes [VHH(T) or VHH(P)], respectively, were used as HER2 anchoring moieties. Optimised high‐FHR4 valence heteromultimeric immunoconjugates [FHR4/VHH(T) or FHR4/VHH(P)] were selected by sequential cell cloning and a selective multistep His‐Trap purification. Optimised FHR4‐heteromultimeric immunoconjugates successfully overcame FH‐mediated complement inhibition threshold, causing increased C3b deposition on SK‐OV‐3, BT474 and SK‐BR3 tumour cells, and increased formation of lytic membrane attack complex densities and complement‐dependent cytotoxicity (CDC). CDC varies according to the pattern expression and densities of membrane‐anchored complement regulatory proteins on tumour cell surfaces. In addition, opsonised BT474 tumour cells were efficiently phagocytosed by macrophages through complement‐dependent cell‐mediated cytotoxicity. We showed that the degree of FHR4‐multivalency within the multimeric immunoconjugates was the key element to efficiently compete and deregulate FH and FH‐mediated convertase decay locally on tumour cell surface. FHR4 can thus represent a novel therapeutic molecule, when expressed as a multimeric entity and associated with an anchoring system, to locally shift the complement steady‐state towards activation on tumour cell surface.
Comparison of Novel, Bach Mai Boston Tool (BBT) and the Patient-Generated Subjective Global Assessment (PG-SGA) for Oncology Inpatients

Oncology inpatients are at high risk of malnutrition. Identification of at risk patients by nutrition screening requires a practical and easy to use tool. The aim of this study was to determine the validity of the Bach Mai Boston Tool (BBT) compared to a ‘gold standard’ full nutrition assessment using the Patient-Generated Subjective Global Assessment (PG-SGA). A cross-sectional study was conducted on 270 oncology inpatients from January to December 2016. Cohen’s Kappa, sensitivity, specificity and ROC analyses were performed. 270 inpatients were included in this study with a mean age of 56.3 ± 12.1 years old. Of these patients, 51.8% were male, and 74.1% had gastrointestinal cancer. The mean body mass index of patients was 20.6 ± 3.0 kg/m2. The PG-SGA tool identified 146 (54.1%) malnourished patients, while the BBT identified 105 (39.9%) malnourished patients. The BBT had a medium consistency, with a Kappa value of 0.6. Using a cut-off point of ≥ 4, the BBT had a sensitivity of 87.7% and a specificity of 72.6%. On the other hand, a BBT with a cut-off point ≥ 5 resulted in a sensitivity of 67.1%, a specificity of 94.4%, and an AUC of 0.81. The BBT is a practical, informative and valid tool for detecting malnutrition in hospitalized oncology patients. We recommend using a cut-off point of 4 for screening the risk of malnutrition for oncology inpatients.
Estrogen Deprivation and Myocardial Infarction: Role of Aerobic Exercise Training, Inflammation and Metabolomics

In general, postmenopausal women present higher mortality, and worse prognosis after myocardial infarction (MI) compared to men, due to estrogen deficiency. After MI, cardiovascular alterations occur such as the autonomic imbalance and the pro-inflammatory cytokines increase. In this sense, therapies that aim to minimize deleterious effects caused by myocardial ischemia are important. Aerobic training has been proposed as a promising intervention in the prevention of cardiovascular diseases. On the other hand, some studies have attempted to identify potential biomarkers for cardiovascular diseases or specifically for MI. For this purpose, metabolomics has been used as a tool in the discovery of cardiovascular biomarkers. Therefore, the objective of this work is to discuss the changes involved in ovariectomy, myocardial infarction, and aerobic training, with emphasis on inflammation and metabolism.
Three-dimensional analysis of single molecule FISH in human colon organoids

ABSTRACT The culturing of mini-organs (organoids) in three-dimensions (3D) presents a simple and powerful tool to investigate the principles underlying human organ development and tissue self-organization in both healthy and diseased states. Applications of single molecule analysis are highly informative for a comprehensive understanding of the complexity underlying tissue and organ physiology. To fully exploit the potential of single molecule technologies, the adjustment of protocols and tools to 3D tissue culture is required. Single molecule RNA fluorescence in situ hybridization (smFISH) is a robust technique for visualizing and quantifying individual transcripts. In addition, smFISH can be employed to study splice variants, fusion transcripts as well as transcripts of multiple genes at the same time. Here, we develop a 3-day protocol and validation method to perform smFISH in 3D in whole human organoids. We provide a number of applications to exemplify the diverse possibilities for the simultaneous detection of distinct mRNA transcripts, evaluation of their spatial distribution and the identification of divergent cell lineages in 3D in organoids. Summary: We present a sensitive single-molecule (sm)FISH application for the identification of individual mRNA transcripts and their spatial distribution in 3D in whole human colon organoids.
Comparing the Impact of Cancer and Treatment-Related Effects on Psychological Well-being and Quality of Life Between Hong Kong Survivors of Childhood Solid Tumors and Leukemia

Background Evidence shows that survivors of solid tumors have a lower survival rate and shorter disease-free survival time than survivors of leukemia. However, the psychological well-being and health-related quality of life (HRQOL) of these 2 groups of cancer survivors have not been compared. Objective To examine and compare the impact of cancer and treatment-related effects on psychological well-being and HRQOL between survivors of childhood solid tumors and leukemia. Methods We conducted a cross-sectional study involving 65 Hong Kong survivors of solid tumors and 70 survivors of leukemia aged 8 to 18 years who had their medical follow-up in a pediatric outpatient clinic. Participants’ depressive symptoms, self-esteem, and HRQOL were assessed. Twenty-two survivors of childhood solid tumors and 15 survivors of childhood leukemia were then selected for semistructured interviews. Results Survivors of childhood solid tumors reported significantly higher mean scores for depressive symptoms, and lower mean self-esteem and HRQOL scores than survivors of childhood leukemia. Qualitative data revealed that survivors of childhood solid tumors faced more challenges in their daily life than survivors of childhood leukemia. Conclusions Survivors of childhood solid tumors reported poorer psychological well-being and HRQOL than survivors of childhood leukemia. This vulnerable group warrants more attention and support. Implications for Practice It is vital for healthcare professionals to understand the impact of cancer and treatment-related effects in the context of different types of cancer. This will facilitate development and evaluation of appropriate psychological interventions to promote psychological well-being and HRQOL among childhood cancer survivors.
Physiological and Transcriptomic Changes during the Early Phases of Adventitious Root Formation in Mulberry Stem Hardwood Cuttings

The initiation and induction of root primordia are of great importance for adventitious root (AR) formation in cutting propagation of horticultural and forestry crops. However, the underlying mechanisms orchestrating these early phases of AR formation remain largely unexplored. Here, we investigated the physiological and transcriptomic changes during the early AR phases in mulberry stem hardwood cuttings. The results showed that the concentrations of soluble proteins increased, whereas concentrations of soluble sugars and starch were decreased. Indole-3-acetic acid (IAA) and zeatin had a rapid transit peak at 6 h after planting (hAP) and declined thereafter. The activities of peroxidase and catalase persistently increased and indole-3-acetic acid oxidase was maintained at a higher stable level from 0 hAP, while the activities of polyphenol oxidase fluctuated with soluble phenolics and IAA levels. The comparative transcriptome identified 4276 common genes that were differentially regulated at −6, 0 and 54 hAP. They were separated into five clusters with distinct biological functions such as defense response and photosynthesis. Considerable common genes were assigned to pathways of sugar metabolism, mitogen-activated protein kinase, and circadian rhythm. The gene co-expression network analysis revealed three major co-expressed modules involved in stress responses, hormone signaling, energy metabolism, starch metabolism, and circadian rhythm. These findings demonstrate the positive effect of auxin on AR induction, and uncovered the crucial roles of stress responses, hormone signaling and circadian rhythm in coordinating the physiological changes during the early phases of AR formation in mulberry stem hardwood cuttings.
Pan-Canadian standards for cancer surgery

About the Canadian Partnership Against Cancer The Canadian Partnership Against Cancer (CPAC) is an independent organization funded by the federal government to accelerate action on cancer control for all Canadians. As the steward of the Canadian Strategy for Cancer Control (the Strategy), the Partnership works with Canada’s cancer community to take action to ensure fewer people get cancer, more people survive cancer and those living with the disease have a better quality of life. This work is guided by the Strategy, which was refreshed for 2019 to 2029, and will help drive measurable change for all Canadians affected by cancer. The Strategy includes 5 priorities that will tackle the most pressing challenges in cancer control as well as distinct First Nations, Inuit and Métis Peoples–specific priorities and actions reflecting Canada’s commitment to reconciliation. A specific action in the Strategy calls for reducing the differences in practice and service delivery by setting standards for high-quality care and promoting their adoption. The CPAC will oversee the implementation of the priorities in collaboration with organizations and individuals on the front lines of cancer care: the provinces and territories; health care professionals; people living with cancer and those who care for them; First Nations, Inuit and Métis communities; governments and organizations; and its funder, Health Canada. Learn more about the Partnership and the refreshed Strategy at www.cancerstrategy. ca.
A NOVEL APPLICATION OF MACHINE LEARNING METHODS TO MODEL MICROCONTROLLER UPSET DUE TO INTENTIONAL ELECTROMAGNETIC INTERFERENCE

A novel application of support vector machines (SVMs), artificial neural networks (ANNs) , and Gaussian processes (GPs) for machine learning (GPML) to model microcontroller unit (MCU) upset due to intentional electromagnetic interference (IEMI) is presented. In this approach, an MCU performs a counting operation (0-7) while electromagnetic interference in the form of a radio frequency (RF) pulse is direct-injected into the MCU clock line. Injection times with respect to the clock signal are the clock low, clock rising edge, clock high, and the clock falling edge periods in the clock window during which the MCU is performing initialization and executing the counting procedure. The intent is to cause disruption in the counting operation and model the probability of effect (PoE) using machine learning tools. Five experiments were executed as part of this research, each of which contained a set of 38,300 training points and 38,300 test points, for a total of 383,000 total points with the following experiment variables: injection times with respect to the clock, injected RF power, injected RF pulse width, and injected RF frequency. For the 191,500 training points, the average training error was 12.47%, while for the 191,500 test points the average test error was 14.85%, meaning that on average, the machine was able to predict MCU upset with an 85.15% accuracy. Leaving out the results for the worst-performing model (SVM with a linear kernel), the test prediction accuracy for the remaining machines is almost 89%. All three machine learning methods (ANNs, SVMs, and GPML) showed excellent and consistent results in their ability to model and predict the PoE on an MCU due to IEMI, with the GP approach performing best during training with a 7.43% average training error, while the ANN technique was most accurate during test with a 10.80% error.