Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of AMPK Promotes Maturation of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (hiPSC-CMs) are a promising cell source for disease modeling, myocardial regeneration, and drug assessment. However, hiPSC-CMs have certain immature fetal CM-like properties that are different from the characteristics of adult CMs in several aspects, including cellular structure, mitochondrial function, and metabolism, thus limiting their applications. Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) is an energy-sensing protein kinase involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in cardiomyocytes. This study investigated the effects of AMPK on the maturation of hiPSC-CMs. Activation of AMPK in hiPSC-CMs significantly increased the expression of CM-specific markers and resulted in a more mature myocardial structure compared to that in the control cells. We found that activation of AMPK improved mitochondrial oxidative phosphorylation (OxPhos) and the oxygen consumption rate (OCR). Additionally, our data demonstrated that activation of AMPK increased mitochondrial fusion to promote the maturation of mitochondrial structure and function. Overall, activation of AMPK is an effective approach to promote hiPSC-CMs maturation, which may enhance the utility of hiPSC-CMs in clinical applications.
Ammonia Sanitisation of Human Excreta Treatment Technology for Production of Fertiliser

Safe reuse of plant nutrients from human excreta increases the sustainability of society and promotes health, both by decreasing disease transmission and by increasing agricultural production. This thesis examined ammonia sanitisation as a treatment method to produce a hygienically safe fertiliser from source-separated urine and faeces. Salmonella spp. and E. coli O157:H7 were inactivated to a high degree even at low NH3 concentrations and temperatures. It was possible to model Salmonella spp. inactivation using these two parameters. Salmonella spp. inactivation is suggested to be verified by determining inactivation of faecal coliforms. Between NH3 concentrations 20 and 60 mM, a sharp decrease in inactivation was observed at 24 oC or below for Enterococcus spp. , bacteriophages and Ascaris eggs, with insignificant inactivation of the latter during 6 months. Urine contains sufficiently high total ammonia concentration and pH for selfsanitisation. Keeping the urine as concentrated as possible proved critical in achieving NH3 concentrations that inactivated Ascaris eggs. Sun exposure increased urine temperature and NH3 and shortened treatment time, and is feasible when urine containers are small. Urea treatment of faeces increased pH and total ammonia concentrations, both contributing to formation of NH3. The final value and stability of the pH achieved depended on initial pH and other material properties, but increased with increasing urea addition. At high pH caused by ash addition, urea was not degraded. When urea was added alone, it could not be confirmed that it was fully degraded. Organism inactivation was always faster in urea-treated faeces compared with untreated faeces. Urea treatment substantially shortened treatment time compared with storage, especially at the higher temperatures studied (24 and 34 oC). Sanitation systems that collect urine and faeces separate and sanitise them by ammonia permit a high degree of hygienically safe plant nutrient reuse.
YWHAG Mutations Cause Childhood Myoclonic Epilepsy and Febrile Seizures: Molecular Sub-regional Effect and Mechanism

YWHAG, which encodes an adapter protein 14-3-3γ, is highly expressed in the brain and regulates a diverse range of cell signaling pathways. Previously, eight YWHAG mutations have been identified in patients with epileptic encephalopathy (EE). In this study, using trios-based whole exome sequencing, we identified two novel YWHAG mutations in two unrelated families with childhood myoclonic epilepsy and/or febrile seizures (FS). The identified mutations included a heterozygous truncating mutation (c.124C>T/p.Arg42Ter) and a de novo missense mutation (c.373A>G/p.Lys125Glu). The two probands experienced daily myoclonic seizures that were recorded with ictal generalized polyspike-slow waves, but became seizure-free with simple valproate treatment. The other affected individuals presented FS. The truncating mutation was identified in the family with six individuals of mild phenotype, suggesting that YWHAG mutations of haploinsufficiency are relatively less pathogenic. Analysis on all missense mutations showed that nine mutations were located within 14-3-3γ binding groove and another mutation was located at residues critical for dimerization, indicating a molecular sub-regional effect. Mutation Arg132Cys, which was identified recurrently in five patients with EE, would have the strongest influence on binding affinity. 14-3-3γ dimers supports target proteins activity. Thus, a heterozygous missense mutation would lead to majority dimers being mutants; whereas a heterozygous truncating mutation would lead to only decreasing the number of wild-type dimer, being one of the explanations for phenotypical variation. This study suggests that YWHAG is potentially a candidate pathogenic gene of childhood myoclonic epilepsy and FS. The spectrum of epilepsy caused by YWHAG mutations potentially range from mild myoclonic epilepsy and FS to severe EE.
Common Vetch, Valuable Germplasm for Resilient Agriculture: Genetic Characterization and Spanish Core Collection Development

Common vetch (Vicia sativa L.) is a legume used for animal feed because of its high protein content and great capacity for nitrogen fixation, making this crop relevant in sustainable agriculture. The Spanish vetch collection, conserved at the Spanish Plant Genetic Resources Center (CRF), is one of the largest collections of this species worldwide, including landraces, wild relatives mainly collected in Spain, and commercial cultivars, but also accessions of international origin. The analysis of the genetic diversity of this material, whose genome has not been sequenced yet, and the assembly of a representative collection could play a pivotal role in conserving and exploiting these genetic resources in breeding programs mainly in those focused on consequences and demands of climate change. In this work, a set of 14 simple sequence repeat (SSR) reference alleles for genetic diversity analysis of the CRF vetch collection has been developed, used for genotyping more than 545 common vetch accessions from all over the world and validated. All the tested markers were polymorphic for the analyzed accessions. Overall, at least 86 different loci were identified with 2–11 alleles per locus with an average of 6.1 alleles per locus. Also, the analyses of the generated SSR database support that most of these SSR markers are transferable across closely related species of Vicia genus. Analysis of molecular variance revealed that wild relatives have a higher genetic diversity than landraces. However, cultivars have similar diversity than landraces, indicating that genetic variability has been barely lost due to the breeding of this legume. Low differences of genetic variations between Spanish and non-Spanish accessions have been observed, suggesting a high degree of diversity within Spanish genotypes, which provide 95% of the total genetic variation, so we have focused our efforts on characterizing genotypes of Spanish origin that were further studied using storage protein profiles. Based on SSR, seed protein profiles, and agromorphological and passport data, a vetch core collection (VCC) containing 47 V. sativa accessions of Spanish origin has been established. In this collection, the characterization has been expanded using ISSR markers, and it has been reevaluated with new agromorphological data, including drought tolerance characters. This VCC presents a minimum loss of genetic diversity concerning the total collection and constitutes an invaluable material that can be used in future breeding programs for direct use in a resilient agricultural system.
Case Report: Early Breast Cancer Recurrence Mimicking BIA-ALCL in a Patient With Multiple Breast Procedures

Breast reconstruction plays a fundamental role in the therapeutic process of breast cancer treatment and breast implants represents the leading breast reconstruction strategy. Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL), locoregional recurrence in the skin flap, and skin flap necrosis are well-known complications following mastectomy and immediate breast reconstruction (IBR). We report a case of locoregional cancer recurrence in the mastectomy flap mimicking BIA-ALCL, in a patient who underwent 6 breast procedures in four facilities across 15 years including immediate breast reconstruction with macrotextured breast implants. Despite the rate and onset of the disease, clinicians should be aware of BIA-ALCL. Due to the risk of false negative results of fine needle aspiration, clinical suspicion of BIA-ALCL should drive clinicians' choices, aside from cytological results. In the present case, surgical capsulectomy of the abnormal periprosthesic tissue revealed locoregional recurrence.
Evaluating the Benefits of Bayesian Hierarchical Methods for Analyzing Heterogeneous Environmental Datasets: A Case Study of Marine Organic Carbon Fluxes

Large compilations of heterogeneous environmental observations are increasingly available as public databases, allowing researchers to test hypotheses across datasets. Statistical complexities arise when analyzing compiled data due to unbalanced spatial sampling, variable environmental context, mixed measurement techniques, and other reasons. Hierarchical Bayesian modeling is increasingly used in environmental science to describe these complexities, however few studies explicitly compare the utility of hierarchical Bayesian models to simpler and more commonly applied methods. Here we demonstrate the utility of the hierarchical Bayesian approach with application to a large compiled environmental dataset consisting of 5,741 marine vertical organic carbon flux observations from 407 sampling locations spanning eight biomes across the global ocean. We fit a global scale Bayesian hierarchical model that describes the vertical profile of organic carbon flux with depth. Profile parameters within a particular biome are assumed to share a common deviation from the global mean profile. Individual station-level parameters are then modeled as deviations from the common biome-level profile. The hierarchical approach is shown to have several benefits over simpler and more common data aggregation methods. First, the hierarchical approach avoids statistical complexities introduced due to unbalanced sampling and allows for flexible incorporation of spatial heterogeneitites in model parameters. Second, the hierarchical approach uses the whole dataset simultaneously to fit the model parameters which shares information across datasets and reduces the uncertainty up to 95% in individual profiles. Third, the Bayesian approach incorporates prior scientific information about model parameters; for example, the non-negativity of chemical concentrations or mass-balance, which we apply here. We explicitly quantify each of these properties in turn. We emphasize the generality of the hierarchical Bayesian approach for diverse environmental applications and its increasing feasibility for large datasets due to recent developments in Markov Chain Monte Carlo algorithms and easy-to-use high-level software implementations.
Electrochemical Detection of Serum Antibodies Against Mycobacterium avium Subspecies paratuberculosis

Mycobacterium avium subsp. paratuberculosis (MAP) causes a chronic inflammatory intestinal disease, called Johne's disease (JD) in many ruminants. In the dairy industry, JD is responsible for significant economic losses due to decreased milk production and premature culling of infected animals. Test-and-cull strategy in conjunction with risk management is currently recommended for JD control in dairy herds. However, current diagnostic tests are labor-intensive, time-consuming, and/or too difficult to operate on site. In this study, we developed a new method for the detection of anti-M. paratuberculosis antibodies from sera of M. paratuberculosis-infected animals. M. paratuberculosis antigen-coated magnetic beads were sequentially reacted with bovine serum followed by a horseradish peroxidase (HRP)-labeled secondary antibody. The reaction of HRP with its substrate was then quantitatively measured electrochemically using a redox-active probe, ferrocyanide. After optimization of electrochemical conditions and concentration of the redox-active probe, we showed that the new electrochemical detection method could distinguish samples of M. paratuberculosis-infected cattle from those of uninfected cattle with greater separation between the two groups of samples when compared with a conventional colorimetric testing method. Since electrochemical detection can be conducted with an inexpensive, battery-operated portable device, this new method may form a basis for the development of an on-site diagnostic system for JD.
A New Pair of Watchful Eyes for Students in Online Courses

While the recent technological advancements have enabled instructors to deliver mathematical concepts and theories beyond the physical boundaries innovatively and interactively, poor performance and low success rate in mathematic courses have always been a major concern of educators. More specifically, in an online learning environment, where students are not physically present in the classroom and access course materials over the network, it is toilsome for course coordinators to track and monitor every student’s academic learning and experiences. Thus, automated student performance monitoring is indispensable since it is easy for online students, especially those underperforming, to be “out of sight,” hence getting derailed and off-track. Since student learning and performance are evolving over time, it is reasonable to consider student performance monitoring as a time-series problem and implement a time-series predictive model to forecast students’ educational progress and achievement. This research paper presents a case study from a higher education institute where interaction data and course achievement of a previously offered online course are used to develop a time-series predictive model using a Long Short-Term Memory network, a special kind of Recurrent Neural Network architecture. The proposed model makes predictions of student status at any given time of the semester by examining the trend or pattern learned in the previous events. The model reported an average classification accuracy of 86 and 84% with the training dataset and testing dataset, respectively. The proposed model is trialed on selected online math courses with exciting yet dissimilar trends recorded.
Spontaneous Afferent Activity Carves Olfactory Circuits

Electrical activity has a key role in shaping neuronal circuits during development. In most sensory modalities, early in development, internally generated spontaneous activity sculpts the initial layout of neuronal wiring. With the maturation of the sense organs, the system relies more on sensory-evoked electrical activity. Stimuli-driven neuronal discharge is required for the transformation of immature circuits in the specific patterns of neuronal connectivity that subserve normal brain function. The olfactory system (OS) differs from this organizational plan. Despite the important role of odorant receptors (ORs) in shaping olfactory topography, odor-evoked activity does not have a prominent role in refining neuronal wiring. On the contrary, afferent spontaneous discharge is required to achieve and maintain the specific diagram of connectivity that defines the topography of the olfactory bulb (OB). Here, we provide an overview of the development of olfactory topography, with a focus on the role of afferent spontaneous discharge in the formation and maintenance of the specific synaptic contacts that result in the topographic organization of the OB.
Comparative Efficacy of Seven Kinds of Chinese Medicine Injections in Acute Lung Injury and Acute Respiratory Distress Syndrome: A Network Meta-analysis of Randomized Controlled Trials

Background: Chinese medicine injection is wildly used in Acute Lung Injury and Acute respiratory distress syndrome (ALI/ARDS) treatment. However, what kinds of CMIs are more effective in the ALI/ARDS treatment is uncertain. Objectives: Compare the efficacy of different CMIs to identify the optimal one for the therapy of ALI/ARDS patients. Data sources: We searched the data up to April 30, 2020 from MEDLINE, EMBASE, The Cochrane Library, Web of Science, the China Science Journal Citation Report (VIP database), WanFang and the China National Knowledge Infrastructure Study selection: Randomized Clinical Trials assessed at least one of the following outcomes: mortality, Oxygenation Index, length of ICU stay, mechanical ventilation duration, APACHEⅡ score, SOFA score and Murray score, for adult patients of ALI/ADRS. Eligible Studies should also use CMIs as complementary therapies in addition to the standard treatment. Data extraction and synthesis: Two reviewers independently assessed the data. Then, we used a Bayesian random-effects network meta-analysis for data synthesis. Results: Twenty-six studies were selected (involved 2073 participants). Seven kinds of CMIs were evaluated. Compared with standard treatment, Xuebijing is associated with lower mortality. Tanreqing and Xuebijing have the best effect on improving the Oxygenation Index. Huangqi, Danshen, Tanreqing and Xuebijing can significantly reduce the APACHE II score (Huangqi works better than Xuebijing). Huangqi and Xuebijing have the best effect on reducing mechanical ventilation duration and Murray score, while Xuebijing has the best effect on shortening the length of ICU stay. Conclusions: As adjuvant drugs, Xuebijing, Tanreqing and Huangqi show certain effects on treating ALI/ARDS in different aspects.
Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease

Crohn's disease (CD) is a chronic immune-mediated disorder for which there is not a fully effective treatment. Moreover, biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies leads to an effective response in only 60–70% of patients. Our previous data suggested that specific loci polymorphism of the TNFRSF1B, FCGR3A, IL1R, IL1B, and FAS genes could be a predictor of the primary non-response to anti-TNF therapy in CD patients. In this work, we propose to explain this hypothesis by functional analysis in colon biopsies and in a cell culture model. Using the RT-qPCR analysis, we estimated the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes mRNA level in colon biopsies material from inflamed and non-inflamed tissue from 21 CD patients (14 responders and 7 non-responders to anti-TNF therapy) and 6 controls, as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from 14 CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls cultured for 72 h with 10 μg/ml of anti-TNF antibody. Our findings demonstrated a significant down-regulation of TNFRSF1B gene expression in non-responders both in inflamed and in non-inflamed colon tissue, while the expression of the FCGR3A and IL1B genes was significantly up-regulated in non-responders in the inflamed colon region. In vitro research results indicate that the anti-TNF drug induced a significant decrease in TNFRSF1B, FCGR3A, and FAS gene expression in non-responders. These results show that altered TNFRSF1B, FCGR3A, and IL1B genes expression can be a predictor of the primary non-response to anti-TNF therapy in CD patients.
Synthesis of N‐Octyl‐2,7‐dimethoxy‐1,8‐bistrimethylsilyl‐3,6‐dibromocarbazole

Abstract Starting with 2,7‐dimethoxycarbazole, a N‐alkyl‐hexafunctionalized carbazole derivative has been synthesized in only three steps with a good overall yield. N‐Octyl‐1,8‐bistrimethylsilyl‐3,6‐dibromo‐2,7‐dimethoxycarbazole is a new synthon that could be useful for the synthesis of conjugated polymers or bioactive compounds.
Distributed Algorithm Design for Resource Allocation Problems of High-Order Multiagent Systems

A distributed resource allocation problem of high-order systems is studied in this article, where the decisions of agents are constrained by network resources. In contrast to well-known resource allocation problems, this problem involves the high-order dynamics of agents, which results in the ineffectiveness of existing distributed resource allocation algorithms. In order to optimally allocate the network resource, a distributed algorithm is developed via state feedback and gradient descent. Moreover, the convergence of the algorithm is analyzed with the help of convex analysis and Lyapunov stability theory. By the algorithm, the high-order agents globally exponentially converge to the optimal solution. Finally, the algorithm is illustrated by numerical examples.
Reducing negative emotions in children using social robots: systematic review

Background For many children, visiting the hospital can lead to a state of increased anxiety. Social robots are being explored as a possible tool to reduce anxiety and distress in children attending a clinical or hospital environment. Social robots are designed to communicate and interact through movement, music and speech. Objective This systematic review aims at assessing the current evidence on the types of social robots used and their impact on children’s anxiety or distress levels when visiting the hospital for outpatient appointments or planned admissions. Methods Databases such as MEDLINE, PubMed, IEEE Xplore, Web of Science, PsychINFO and Google Scholar were queried for papers published between January 2009 and August 2020 reporting the use of social robots interacting with children in hospital or clinical environments. Results A total of 10 studies were located and included. Across these 10 studies, 7 different types of robots were used. Anxiety and distress were found to be reduced in the children who interacted with a social robot. Conclusions Overall, the evidence suggests that social robots hold a promising role in reducing levels of anxiety or distress in children visiting the hospital. However, research on social robots is at an early stage and requires further studies to strengthen the evidence base. Social robots may reduce stress and anxiety in children admitted to hospital, but better quality research is needed before widespread adoption
Revising the use of potassium (K) in the source apportionment of PM2.5

Abstract Elemental potassium has been extensively used as an indicator of biomass burning in the source apportionment of PM2.5. We present a method to estimate the fraction of potassium associated with biomass burning (Kb) based on a linear regression with iron that can be applied at any site where PM2.5 chemical speciation is available. The estimated fraction has a significantly greater correlation with levoglucosan (R2=0.63), an organic tracer of biomass burning, than total potassium (R2=0.39). We explore temporal and spatial variability of Kb over a period of six years in the Atlanta area. Kb is larger in spring when biomass burning activity is more prevalent and during weekends due to the use of fireplaces in winter and outdoor charcoal cooking in summer. Kb is the predominate form of potassium for the rural site in this study. The use of Kb in a receptor model results in a lower fraction of PM2.5 apportioned to biomass burning and a greater fraction to mobile sources when compared to the use of total K. Results suggest that Kb is a good indicator of biomass burning.