Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioactive coatings on 3D printed polycaprolactone scaffolds for bone regeneration: a novel murine femur defect model for examination of the biomaterial capacity for repair

Bone tissue engineering is a rapidly advancing field that seeks to develop efficacious approaches for treating non-healing fractures and large bone defects. Healing complications arise due to trauma, disease, infection, aseptic loosening of orthopaedic implants or iatrogenic causes. An ideal biodegradable scaffold would induce and support bone formation until the bone matrix is sufficiently stable to facilitate healing. The current study has examined bone augmentation, using functionalised coated scaffolds, with the hypothesised potential to induce skeletal cell differentiation for the repair of critical-sized bone defects. However, challenges in clinical translation arise from the alterations in cellular microenvironment that are present in the translation from in vitro to in vivo with the application of animal models of progressively increasing size and complexity of the implantation site. 3D printed, porous poly(caprolactone) trimethacrylate (denoted PCL-TMA900) scaffolds were applied within a murine femur defect, stabilised by a polyimide intramedullary pin, to assess the efficacy of select coatings in inducing bone formation. The PCL-TMA900 scaffolds were coated with i) elastin-like polypeptide (ELP), ii) poly(ethyl acrylate)/fibronectin/bone morphogenetic protein-2 (PEA/FN/BMP-2), iii) both ELP and PEA/FN/BMP-2 concurrently, or iv) Laponite™ nanoclay binding BMP-2, as bioactive coatings. The murine femur defect model was refined to assess the coated PCL-TMA900 scaffolds in an osseous defect, with sequential microcomputed tomography (µCT) and histological analysis of the new bone tissue. Overall, PCL-TMA900 was found to be an optimal robust, biocompatible, 3D printable scaffold material. All PCL-TMA900 scaffolds, uncoated and coated, showed integration with the femur. The PCL-TMA900 scaffold coated with the nanoclay material Laponite™ and BMP-2 induced consistent, significant bone formation compared to the uncoated PCL-TMA900 scaffold. Bone formation was observed within the pores of the Laponite/BMP-2 coated scaffold. Critically, no heterotopic bone formation was observed as the BMP-2 was retained around the scaffold and not released into the tissues, producing bone around the scaffold in the desired shape and volume, compared to bone formation observed with the positive control (collagen sponge/BMP-2 construct). In comparison, the ELP coated and PEA/FN/BMP-2 scaffolds did not demonstrate significant or consistent bone formation compared to uncoated PCL-TMA900 control scaffolds. In summary, nanoclay Laponite™/BMP-2 coated PCL-TMA900 scaffolds offer a biodegradable, osteogenic construct for bone augmentation with potential for development into a large scale polymer scaffold for translation to the clinic.
Encompassing view of spatial and single-cell RNA-seq renews the role of the microvasculature in human atherosclerosis

Atherosclerosis is a pervasive contributor to cardiovascular diseases including ischemic heart disease and stroke. Despite the advance and success of effective lipid lowering-therapies and hypertensive agents, the residual risk of an atherosclerotic event remains high and improving disease understanding and development of novel therapeutic strategies has proven to be challenging. This is largely due to the complexity of atherosclerosis with a spatial interplay of multiple cell types within the vascular wall. Here, we generated an integrative high-resolution map of human atherosclerotic plaques by combining single-cell RNA-seq from multiple studies and novel spatial transcriptomics data from 12 human specimens to gain insights into disease mechanisms. Comparative analyses revealed cell-type and atherosclerosis-specific expression changes and associated alterations in cell-cell communication. We highlight the possible recruitment of lymphocytes via different endothelial cells of the vasa vasorum, the migration of vascular smooth muscle cells towards the lumen to become fibromyocytes, and cell-cell communication in the plaque, indicating an intricate cellular interplay within the adventitia and the subendothelial space in human atherosclerosis.
The ICF syndrome protein CDCA7 harbors a unique DNA-binding domain that recognizes a CpG dyad in the context of a non-B DNA

CDCA7, encoding a protein with a C-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout the genome. At S phase, CDCA7, but not ICF mutants, is concentrated in constitutive heterochromatin foci, and the formation of such foci can be inhibited by exogenous hemi-methylated non-B DNA bound by the CRD. Binding of the non-B DNA formed in juxtacentromeric regions during DNA replication provides a mechanism by which CDCA7 controls the specificity of DNA methylation.
Structural and mechanistic views of enzymatic, heme-dependent nitrogen-nitrogen bond formation

Molecules with nitrogen-nitrogen (N-N) bonds constitute a large group of clinically important drugs, and various synthetic approaches have been developed to construct functional groups like hydrazines, diazos, pyrazoles, and N-nitrosos. While hundreds of N-N-containing specialized natural metabolites have also been discovered, little is known about the underlying enzymatic mechanisms that have evolved for N-N bond formation. In order to directly form a single N(sp3)-N(sp3) bond, enzymes must reverse the typical nucleophilicity of one nitrogen. Here, we report structural and mechanistic interrogations of the piperazate synthase PipS, a heme-dependent enzyme that catalyzes an N-N bond forming cyclization of N5-OH-L-ornithine to give the non-proteinogenic amino acid L-piperazic acid. We show that PipS can process a variety of N-substituted hydroxylamines, to give either an imine or an N-N bond, in a substrate-specific manner. Using a combination of structural and biochemical experiments, computational studies, and spectroscopic characterization, we propose that heme-dependent dehydration and N-N bond formation in PipS proceed through divergent pathways, which may stem from a shared nitrenoid intermediate that effectively reverses the nucleophilicity of the hydroxylamine nitrogen. Our work expands the current knowledge of enzymatic N-N bond formation, and delineates the catalytic versatility of a heme cofactor, paving the way for future development of genetically encoded biocatalysts for N-N bond formation.
Transgenerational effects of early life stress on the fecal microbiota in mice

Stress in early life can affect the progeny and increase the risk to develop psychiatric and cardiometabolic diseases across generations. The cross-generational effects of early life stress have been modeled in mice and demonstrated to be associated with epigenetic factors in the germline. While stress is known to affect gut microbial features, whether its effects can persist across life and be passed to the progeny is not well defined. Here we show that early postnatal stress in mice shifts the fecal microbial composition (binary Jaccard index) throughout life. Further effects on fecal microbial composition and structure (weighted Jaccard index) are detected in the progeny across two generations. These effects are not accompanied by changes in bacterial metabolites and related predicted metabolic pathways in any generation. These results suggest that changes in the fecal microbial community induced by early life traumatic stress can be perpetuated from exposed parent to the offspring.
Management characteristics of beef cattle production in the Northern Plains and Midwest regions of the United States

A comprehensive life cycle assessment of United States beef will provide benchmarks and identify opportunities for improvement. On-going region-specific data collection is characterizing cattle production practices for a more accurate assessment. This study reports production information obtained via online surveys and on-site visits from 2 of 7 regions: the Northern Plains (Nebraska, North Dakota, and South Dakota) and Midwest (Illinois, Indiana, Iowa, Michigan, Minnesota, Missouri, and Wisconsin). Ranch responses (n = 512) represented 1.6% of beef cows maintained in both regions with operation sizes varying from 1 to 12,500 cows. Feedlot responses (n = 120) represented 9.6 and 3.7% of cattle finished in the Northern Plains and Midwest, respectively. Ranch herd sizes increased and stocking rates decreased moving westward. Average animal BW increased from south to north. Also recorded were bull and replacement heifer numbers; housing facilities; feed production and use; and machinery, energy, and labor use. Feedlot characteristics including entering and final BW, background and finish feeding periods, crop area per animal, and labor were similar across the regions, but the Northern Plains reported larger feedlots than the Midwest. Diets were similar across regions except that slightly more distillers grain and less corn were fed in the Northern Plains. Ninety-three percent of feedlots produced most of their feed (corn grain, corn silage, and alfalfa). Cropland producing feed received most of the manure produced, but a few large feedlots reported composting and export. Information gathered provides production system characteristics and inventory for conducting a comprehensive United States beef life cycle assessment.
Molecular epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa hospital, South Africa

Background An outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. Methods Bacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. Results The outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemase-positive, but four blaOXA-48 isolates were susceptible to carbapenems. BlaNDM-1 (n = 13) and blaOXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. Conclusions The outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.
Young Zambian infants with symptomatic RSV and pertussis infections are frequently prescribed inappropriate antibiotics

Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO's Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care in a cohort of 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia. We prospectively monitored mother/infant pairs across infants' first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for Respiratory syncytial virus (RSV) and Bordetella pertussis. Symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins.
The effects of intermittent hypoxic training on aerobic and anaerobic performance

The aim of the present study was to determine whether short-term intermittent hypoxic training would enhance sea level aerobic and anaerobic performance over and above that occurring with equivalent sea level training. Over a 4-week period, two groups of eight moderately trained team sports players performed 30 min of cycling exercise three times per week. One group trained in normobaric hypoxia at a simulated altitude of 2750 m (FIO2= 0.15), the other group trained in a laboratory under sea level conditions. Each training session consisted of ten 1-min bouts at 80% maximum workload maintained for 2 min (Wmax) during the incremental exercise test at sea level separated by 2-min active recovery at 50% Wmax. Training intensities were increased by 5% after six training sessions and by a further 5% (of original Wmax) after nine sessions. Pre-training assessments of VO2max, power output at onset of 4 mM blood lactate accumulation (OBLA), Wmax and Wingate anaerobic performance were performed on a cycle ergometer at sea level and repeated 4–7 d following the training intervention. Following training there were significant increases (p < 0.01) in VO2max (7.2 vs. 8.0%), Wmax (15.5 vs. 17.8%), OBLA (11.1 vs. 11.9%), mean power (8.0 vs. 6.5%) and peak power (2.9 vs. 9.3%) in both the hypoxic and normoxic groups respectively. There were no significant differences between the increases in any of the above-mentioned performance parameters in either training environment (p>0.05). In addition, neither haemoglobin concentration nor haematocrit were significantly changed in either group (p>0.05). It is concluded that acute exposure of moderately trained subjects to normobaric hypoxia during a short-term training programme consisting of moderate- to high-intensity intermittent exercise has no enhanced effect on the degree of improvement in either aerobic or anaerobic performance. These data suggest that if there are any advantages to training in hypoxia for sea level performance, they would not arise from the short-term protocol employed in the present study.
On the Estimation and Inference of a Cointegrated Regression in Panel Data

The main contribution of this paper is to add to the literature by suggesting a dynamic OLS (DOLS) estimator and providing a serious comparison of the finite sample properties of the OLS, fully modified OLS (FMOLS), and DOLS estimators in panel cointegrated regression models. Monte Carlo results illustrate the sampling behavior of the proposed estimators and show that (1) the OLS estimator has a non-negligible bias in finite samples, (2) the FMOLS estimator does not improve over the OLS estimator in general, and (3) the DOLS outperforms both the OLS and FMOLS estimators.
Towards a Platform-Independent Cooperative Human Robot Interaction System: III An Architecture for Learning and Executing Actions and Shared Plans

Robots should be capable of interacting in a cooperative and adaptive manner with their human counterparts in open-ended tasks that can change in real-time. An important aspect of the robot behavior will be the ability to acquire new knowledge of the cooperative tasks by observing and interacting with humans. The current research addresses this challenge. We present results from a cooperative human-robot interaction system that has been specifically developed for portability between different humanoid platforms, by abstraction layers at the perceptual and motor interfaces. In the perceptual domain, the resulting system is demonstrated to learn to recognize objects and to recognize actions as sequences of perceptual primitives, and to transfer this learning, and recognition, between different robotic platforms. For execution, composite actions and plans are shown to be learnt on one robot and executed successfully on a different one. Most importantly, the system provides the ability to link actions into shared plans, that form the basis of human-robot cooperation, applying principles from human cognitive development to the domain of robot cognitive systems.
Five new things

HIV-associated neurocognitive disorders (HAND) remain an important cause of cognitive dysfunction. Current nomenclature for HAND includes HIVassociated dementia and milder forms known as asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND). ANI and MND remain highly prevalent despite combined antiretroviral therapy (cART). These mild forms of HANDmust be diagnosed through neuropsychological testing. If a patient has HAND, it remains unclear whether using a cART regimen with theoretically superior CNS penetration improves the prognosis. Nevertheless, a CNS penetration effectiveness score for antiretrovirals is available. Other factors to consider when diagnosing and treating HIV infection and HAND include the HIV clade or subtype. Data suggest that HAND occurs more often in association with certain clades, and higher vigilance for cognitive dysfunction may be recommended. Finally, comorbidities, such as diseases associated with advanced age, other infections, and drug abuse, need to be considered as cofactors for cognitive dysfunction and treated accordingly.
Defining architectures for recommended systems for medical treatment. A Systematic Literature Review

This paper presents a Systematic Literature Review(SLR) related to recommender system for medical treatment, aswell as analyze main elements that may provide flexible, accurate,and comprehensive recommendations. To do so, a SLR researchmethodology obey. As a result, 12 intelligent recommendersystems related to prescribing medication were classed dependingto specific criteria. We assessed and analyze these medicinerecommender systems and enumerate the challenges. After studyingselected papers, our study concentrated on two researchquestions concerning the availability of medicine recommendersystems for physicians and the features these systems should have.Further research is encouraged in order to build an intelligentrecommender system based on the features analyzed in this work.
Status and trends of geese (Anser sp., Branta sp.) in the world : A review, updating and evaluation

II existe 15 especes d'oies, Anser sp. , Branta sp. , dans le monde entier. Toutes, sauf une, se reproduisent et hivernent dans l'hemisphere Nord. Elles sont divisees en 67 populations qui, au debut des annees 1990, comptaient au total environ 11 millions d'individus. Les effectifs des populations en question varient de 50 individus a 2 millions d'individus. A l'echelle regionale, les populations les plus importantes se trouvent en Amerique du Nord, celles de taille intermediaire sont dans le Palearctique Occidental et les plus petites dans le Palearctique Oriental (depuis la mer Caspienne vers l'Est). Dans le monde entier, 45 % des populations sont actuellement en augmentation, 25 % sont stables, 18% sont en declin, et pour 12% la tendance est inconnue. Toutefois, sur le plan regional, on observe pour la plupart des populations d'Amerique du Nord et du Palearctique Occidental une tendance a l'augmentation ou a la stabilite, alors que pour la plupart des populations du Palearctique Oriental cette tendance est a la baisse ou inconnue. En Amerique du Nord et dans le Palearctique Occidental, le suivi annuel de la taille de la population a ete realise pour la plupart des populations, alors que dans le Palearctique Oriental il y a de nombreuses lacunes importantes. En Amerique du Nord et dans le Palearctique Occidental on dispose dinstruments/reglementations juridiques nationaux et d'accords internationaux existants ou en preparation, applicables en cas de declin des populations a des niveaux inacceptables. Dans le Palearctique Oriental, ce genre d'accord n'a pas encore ete conclu. Il y a une crainte grandissante, surtout en Amerique du Nord, qu'a long terme les populations nombreuses, et en augmentation, pourraient provoquer le surpâturage de leur habitat de nidification, ce qui menerait a un declin important de leurs effectifs dans un futur proche. A court terme, a part quelques rares exceptions, les situations des populations d'oies d'Amerique du Nord et du Palearctique Occidental sont bonnes, et l'attention et les efforts de conservation devraient plutot viser a sauvegarder les petites populations et celles qui sont en declin ailleurs. Il conviendrait donc d'accorder la plus grande priorite possible a la recherche et aux mesures de conservation destinees a preserver les petites populations declinantes d'oies qui se reproduisent et hivernent dans le Palearctique Oriental. Au niveau mondial, les especes les plus menacees sont la bernache nene, Branta sandvicensis, l'oie naine, Anser erythropus, et l'oie cygnoide, Anser cygnoides. En ce qui concerne l'oie naine, a cause d'un manque de donnees recentes sur leurs populations, il y a particulierement urgence a mettre en oeuvre des etudes coordonnees sur un plan international.
Newly Isolated Paenibacillus tyrﬁs sp. nov., from Malaysian Tropical Peat Swamp Soil with Broad Spectrum Antimicrobial Activity

T when compared to its closely related type species, we propose that strain MSt1 T represents a novel species within the genus of Paenibacillus , for which the name Paenibacillus tyrﬁs sp. nov. ( = DSM 100708 T = MCCC 1K01247 T ) is proposed.