Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo Bioluminescence Imaging in a Rabbit Model of Orthopaedic Implant-Associated Infection to Monitor Efficacy of an Antibiotic-Releasing Coating

Background: In vivo bioluminescence imaging (BLI) provides noninvasive monitoring of bacterial burden in animal models of orthopaedic implant-associated infection (OIAI). However, technical limitations have limited its use to mouse and rat models of OIAI. The goal of this study was to develop a larger, rabbit model of OIAI using in vivo BLI to evaluate the efficacy of an antibiotic-releasing implant coating. Methods: A nanofiber coating loaded with or without linezolid-rifampin was electrospun onto a surgical-grade locking peg. To model OIAI in rabbits, a medial parapatellar arthrotomy was performed to ream the femoral canal, and a bright bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into the canal, followed by retrograde insertion of the coated implant flush with the articular surface. In vivo BLI signals were confirmed by ex vivo colony-forming units (CFUs) from tissue, bone, and implant specimens. Results: In this rabbit model of OIAI (n = 6 rabbits per group), implants coated without antibiotics were associated with significantly increased knee width and in vivo BLI signals compared with implants coated with linezolid-rifampin (p < 0.001 and p < 0.05, respectively). On day 7, the implants without antibiotics were associated with significantly increased CFUs from tissue (mean [and standard error of the mean], 1.4 × 108 ± 2.1 × 107 CFUs; p < 0.001), bone (6.9 × 106 ± 3.1 × 106 CFUs; p < 0.05), and implant (5.1 × 105 ± 2.2 × 105 CFUs; p < 0.05) specimens compared with implants with linezolid-rifampin, which demonstrated no detectable CFUs from any source. Conclusions: By combining a bright bioluminescent MRSA strain with modified techniques, in vivo BLI in a rabbit model of OIAI demonstrated the efficacy of an antibiotic-releasing coating. Clinical Relevance: The new capability of in vivo BLI for noninvasive monitoring of bacterial burden in larger-animal models of OIAI may have important preclinical relevance.
YfmK is an Nε-lysine acetyltransferase that directly acetylates the histone-like protein HBsu in Bacillus subtilis

Significance Nε-lysine acetylation is a dynamic regulatory posttranslational modification that affects hundreds of proteins in all three domains of life. In bacteria, acetylated proteins can be found in many essential pathways, and may also be important for virulence in pathogenic species. However, the biological relevance of the overwhelming majority of these acetylation events remains poorly characterized. Here, we discover that acetylation of the histone-like protein HBsu regulates its ability to control nucleoid compaction, and we identify the second protein acetyltransferase in Bacillus subtilis. Moving forward, the targeting of bacterial protein acetylation may be exploited to aid in the design of novel therapeutics, as it has been successful in the treatment of certain cancers and latent viral and fungal infections. Nε-lysine acetylation is an abundant and dynamic regulatory posttranslational modification that remains poorly characterized in bacteria. In bacteria, hundreds of proteins are known to be acetylated, but the biological significance of the majority of these events remains unclear. Previously, we characterized the Bacillus subtilis acetylome and found that the essential histone-like protein HBsu contains seven previously unknown acetylation sites in vivo. Here, we investigate whether acetylation is a regulatory component of the function of HBsu in nucleoid compaction. Using mutations that mimic the acetylated and unacetylated forms of the protein, we show that the inability to acetylate key HBsu lysine residues results in a more compacted nucleoid. We further investigated the mechanism of HBsu acetylation. We screened deletions of the ∼50 putative GNAT domain-encoding genes in B. subtilis for their effects on DNA compaction, and identified five candidates that may encode acetyltransferases acting on HBsu. Genetic bypass experiments demonstrated that two of these, YfmK and YdgE, can acetylate Hbsu, and their potential sites of action on HBsu were identified. Additionally, purified YfmK was able to directly acetylate HBsu in vitro, suggesting that it is the second identified protein acetyltransferase in B. subtilis. We propose that at least one physiological function of the acetylation of HBsu at key lysine residues is to regulate nucleoid compaction, analogous to the role of histone acetylation in eukaryotes.
Using growth factors in human extraction sockets: a histologic and histomorphometric evaluation of short-term healing.

PURPOSE Ridge preservation protocols reduce crestal remodeling after tooth extraction. There is insufficient evidence on bone grafting in combination with platelet-rich plasma (PRP) or recombinant human platelet-derived growth factor (rhPDGF-BB). The aim of this study is to evaluate healing of grafted and nongrafted sockets and the effect of PRP and rhPDGF-BB on early remodeling. MATERIALS AND METHODS Forty-one patients whose treatment plan included extraction of anterior or premolar teeth were randomized into four groups. Group 1: collagen plug (control). Group 2: mineralized freeze-dried bone allograft (FDBA)/β-tricalcium phosphate (β-TCP)/collagen plug. Group 3: FDBA/β-TCP/PRP/collagen plug. Group 4: FDBA/β-TCP/rhPDGF-BB/collagen plug. At 8 weeks, a core was harvested from the center of 41 sockets. Histomorphometric analysis took place. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means. Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. A P value < . 05 was considered statistically significant. RESULTS ANOVA did not indicate statistical significance in age, gender, smoking, ethnicity, or race distribution. Significant differences in tissue distribution were identified between groups and between different thirds of harvested core. More new bone and amorphous organic matrix was noted in the control group. In sites where bone graft was combined with growth factors, the amount of residual particles was less than in sites where bone graft was used alone. CONCLUSIONS Inclusion of bone replacement graft suppressed new bone formation during early healing. Inclusion of PRP and rhPDGF-BB produced less residual bone graft material, indicating more rapid turnover of bone graft. All treatment modalities achieved a significant amount of new vital bone at 8 weeks postextraction.
Quadratic penalty method for intensity-based deformable image registration and 4DCT lung motion recovery.

Intensity-based deformable image registration (DIR) requires minimizing an image dissimilarity metric. Imaged anatomy, such as bones and vasculature, as well as the resolution of the digital grid, can often cause discontinuities in the corresponding objective function. Consequently, the application of a gradient-based optimization algorithm requires a preprocessing image smoothing to ensure the existence of necessary image derivatives. Simple block matching (exhaustive search) methods do not require image derivative approximations, but their general effectiveness is often hindered by erroneous solutions (outliers). Block match methods are therefore often coupled with a statistical outlier detection method to improve results. PURPOSE The purpose of this work is to present a spatially accurate, intensity-based DIR optimization formulation that can be solved with a straightforward gradient-free quadratic penalty algorithm and is suitable for 4D thoracic computed tomography (4DCT) registration. Additionally, a novel regularization strategy based on the well-known leave-one-out robust statistical model cross-validation method is introduced. METHODS The proposed Quadratic Penalty DIR (QPDIR) method minimizes both an image dissimilarity term, which is separable with respect to individual voxel displacements, and a regularization term derived from the classical leave-one-out cross-validation statistical method. The resulting DIR problem lends itself to a quadratic penalty function optimization approach, where each subproblem can be solved by straightforward block coordinate descent iteration. RESULTS The spatial accuracy of the method was assessed using expert-determined landmarks on ten 4DCT datasets available on www.dir-lab.com. The QPDIR algorithm achieved average millimeter spatial errors between 0.69 (0.91) and 1.19 (1.26) on the ten test cases. On all ten 4DCT test cases, the QPDIR method produced spatial accuracies that are superior or equivalent to those produced by current state-of-the-art methods. Moreover, QPDIR achieved accuracies at the resolution of the landmark error assessment (i.e., the interobserver error) on six of the ten cases. CONCLUSION The QPDIR algorithm is based on a simple quadratic penalty function formulation and a regularization term inspired by leave-one-out cross validation. The formulation lends itself to a parallelizable, gradient-free, block coordinate descent numerical optimization method. Numerical results indicate that the method achieves a high spatial accuracy on 4DCT inhale/exhale phases.
Effect of exercise timing on elevated postprandial glucose levels.

There is no consensus regarding optimal exercise timing for reducing postprandial glucose (PPG). The purpose of the present study was to determine the most effective exercise timing. Eleven participants completed four different exercise patterns 1) no exercise; 2) preprandial exercise (jogging); 3) postprandial exercise; and 4) brief periodic exercise intervention (three sets of 1-min jogging + 30 s of rest, every 30 min, 20 times total) in a random order separated by a minimum of 5 days. Preprandial and postprandial exercise consisted of 20 sets of intermittent exercise (1 min of jogging + 30 s rest per set) repeated 3 times per day. Total daily exercise volume was identical for all three exercise patterns. Exercise intensities were 62.4 ± 12.9% V̇o2peak Blood glucose concentrations were measured continuously throughout each trial for 24 h. After breakfast, peak blood glucose concentrations were lower with brief periodic exercise (99 ± 6 mg/dl) than those with preprandial and postprandial exercise (109 ± 10 and 115 ± 14 mg/dl, respectively, P < 0.05, effect size = 0.517). After lunch, peak glucose concentrations were lower with brief periodic exercise than those with postprandial exercise (97 ± 5 and 108 ± 8 mg/dl, P < 0.05, effect size = 0.484). After dinner, peak glucose concentrations did not significantly differ among exercise patterns. Areas under the curve over 24 h and 2 h postprandially did not differ among exercise patterns. These findings suggest that brief periodic exercise may be more effective than preprandial and postprandial exercise at attenuating PPG in young active individuals.NEW & NOTEWORTHY This was the first study to investigate the effect of different exercise timing (brief periodic vs. preprandial vs. postprandial exercise) on postprandial glucose (PPG) attenuation in active healthy men. We demonstrated that brief periodic exercise attenuated peak PPG levels more than preprandial and postprandial exercise, particularly in the morning. Additionally, PPG rebounded soon after discontinuing postprandial exercise. Thus, brief periodic exercise may be better than preprandial and postprandial exercise at attenuating PPG levels.
Natural hybrids between Tragopogon mirus and T. miscellus (Asteraceae): a new perspective on karyotypic changes following hybridization at the polyploid level.

UNLABELLED PREMISE OF THE STUDY Natural hybrids have formed in Pullman, Washington, United States between the recently formed allotetraploids Tragopogon miscellus and T. mirus. In addition to forming spontaneously, these hybrids are semifertile, propagating via achenes. Previous work indicated that the tetraploid hybrids have genetic contributions from three progenitor diploids: T. dubius, T. pratensis, and T. porrifolius. Because the hybrids contain genomes from three species, they should be karyotypically variable and have very low fertility. To better understand how these hybrids are semifertile, we applied fluorescent probes to determine chromosome composition. • METHODS We sequentially conducted fluorescence and genomic in situ hybridization to generate karyotypes for five hybrid individuals grown from field-collected achenes. • KEY RESULTS All plants had the expected somatic chromosome number (2n = 24), but none showed an additive F1 chromosome complement, i.e., two sets of chromosomes from T. dubius and one set of chromosomes each from T. porrifolius and T. pratensis. No individuals shared an identical karyotype, but chromosomal variation followed a compensatory pattern of substitutions, with all groups of putatively homeologous chromosomes consistently totaling four. • CONCLUSIONS The hybrids appear to be shifting away from a parentally additive F1 karyotype to chromosomal compositions that are mostly, or entirely, disomic. We hypothesize that this process may eventually lead to the elimination of chromosomes from a population and produce a stabilized karyotype distinct from both allotetraploid parents. This work has implications for other hybrids formed between polyploids, in that they may be hard to detect using sequence data alone due to multilateral patterns of chromosome elimination.
Prenatal Diagnosis of Androgen Insensitivity Syndrome

Androgen insensitivity syndrome (AIS) (OMIM 300068) is an X-linked recessive genetic disorder with an XY karyotype that is caused by androgen receptor (AR) defects. We report a prenatal diagnosis case with clinical and molecular findings. The fetal phenotype was female, moreover the autopsy revealed the presence of abdominal testes confirmed by histopathological examination. The AR gene molecular analysis performed on the fetal DNA showed the presence of a c.2493C>T change in exon 4. The single nucleotide change resulted in a Q711X amino acid substitution within the AR ligand-binding domain of the protein that has never been described before in the literature. AIS is an important consideration in pregnancies that show sex discordance in ultrasonography and karyotype results with the opportunity to perform molecular analysis of the AR gene in order to confirm the diagnosis.
Distinct functions of a cGMP-dependent protein kinase in nerve terminal growth and synaptic vesicle cycling

ABSTRACT Sustained neurotransmission requires the tight coupling of synaptic vesicle (SV) exocytosis and endocytosis. The mechanisms underlying this coupling are poorly understood. We tested the hypothesis that a cGMP-dependent protein kinase (PKG), encoded by the foraging (for) gene in Drosophila melanogaster, is critical for this process using a for null mutant, genomic rescues and tissue-specific rescues. We uncoupled the exocytic and endocytic functions of FOR in neurotransmission using a temperature-sensitive shibire mutant in conjunction with fluorescein-assisted light inactivation of FOR. We discovered a dual role for presynaptic FOR, in which FOR inhibits SV exocytosis during low-frequency stimulation by negatively regulating presynaptic Ca2+ levels and maintains neurotransmission during high-frequency stimulation by facilitating SV endocytosis. Additionally, glial FOR negatively regulated nerve terminal growth through TGF-β signalling, and this developmental effect was independent of the effects of FOR on neurotransmission. Overall, FOR plays a critical role in coupling SV exocytosis and endocytosis, thereby balancing these two components to maintain sustained neurotransmission. Summary: This work highlights the multifaceted nature of kinases and provides mechanistic insight into how neurons balance synaptic vesicle exocytosis and endocytosis by identifying a cGMP-dependent protein kinase as a key regulator.
Health professionals in a changing climate: protocol for a scoping review

Introduction Climate change will impose significant health impacts. Although we know health professionals should play a critical role in protecting human health from climate change, their preparedness to engage with these issues worldwide is unclear. This study aims to map the range and nature of existing evidence regarding health professionals’ knowledge, attitudes, perceptions and practices regarding climate change and health impacts and the challenges they face, and identify knowledge gaps to guide future development of research, policy and practices. Methods and analysis We will perform a scoping review based on the six-stage framework proposed by Arksey and O’Malley. Our study includes peer-reviewed literature focusing on any aspect of health professionals’ work regarding climate change and health since 2002 and indexed in MEDLINE/Pubmed, Web of Science, Scopus or Embase. Identified papers will be described and assessed. Thematic analysis will be applied to evaluate and categorise the study findings. Implications and dissemination This is the first scoping review of health professionals’ activities to anticipate and prepare for health impacts attributable to climate change. It will provide evidence regarding the current situations worldwide and gaps in preparedness. The findings can be used to highlight accomplishments to date, identify gaps and further develop good practices for health professionals’ engagement. The results will be published in the peer-reviewed literature and shared at health professional society meetings.
Effects of Nigella sativa oil on ovarian volume, oxidant systems, XIAP and NF-kB expression in an experimental model of diabetes

ABSTRACT We investigated the effects of Nigella sativa oil on ovary volume, nuclear factor-kappaB (NF-κB), X-linked inhibitor of apoptosis protein (XIAP) expression, and serum malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS) and total oxidant status (TOS) levels in diabetic rats. We divided 21 adult female rats into three groups: controls, diabetics and diabetics + N. sativa oil. The diabetics + N. sativa oil group was given 0.2 mg/kg/day N. sativa oil 6 days/week for 4 weeks. NF-κB and XIAP expression was assessed in ovarian sections using immunohistochemistry. The right and left ovary volumes were calculated using stereology. We also measured serum MDA, SOD, TAS and TOS levels. We found that N. sativa oil reduced hyperglycemia, but not to control levels. N. sativa oil also exhibited antioxidant properties as demonstrated by reduced serum TOS and MDA levels, and increased SOD and TAS levels compared to controls. We found no significant difference in total ovarian volume, XIAP or NF-κB expression among the groups, which may be due to the short study period. Our findings suggest that N. sativa oil may be useful for reducing blood glucose levels and elevated oxidant activity in diabetic patients.
Cell lineage-specific genome-wide DNA methylation analysis of patients with paediatric-onset systemic lupus erythematosus

ABSTRACT Patients with paediatric-onset systemic lupus erythematosus (SLE) often present with more severe clinical courses than adult-onset patients. Although genome-wide DNA methylation (DNAm) profiling has been performed in adult-onset SLE patients, parallel data on paediatric-onset SLE are not available. Therefore, we undertook a genome-wide DNAm study in paediatric-onset SLE patients across multiple blood cell lineages. The DNAm profiles of four purified immune cell lineages (CD4 + T cells, CD8 + T cells, B cells and neutrophils) and whole blood were compared in 16 Chinese patients with paediatric-onset SLE and 13 healthy controls using the Illumina HumanMethylationEPIC BeadChip. Comparison of DNAm in whole blood and within each independent cell lineage identified a consistent pattern of loss of DNAm at 21 CpG sites overlapping 15 genes, which represented a robust, disease-specific DNAm signature for paediatric-onset SLE in our cohort. In addition, cell lineage-specific changes, involving both loss and gain of DNAm, were observed in both novel genes and genes with well-described roles in SLE pathogenesis. This study also highlights the importance of studying DNAm changes in different immune cell lineages rather than only whole blood, since cell type-specific DNAm changes facilitated the elucidation of the cell type-specific molecular pathophysiology of SLE.
Polymethylmethacrylate Collagen Gel-Injectable Dermal Filler for Full Face Atrophic Acne Scar Correction.

BACKGROUND/OBJECTIVES This trial evaluated the effectiveness and safety of Bellafill for full-face acne scar treatment. PATIENTS AND METHODS In this open-label, nonrandomized, multicenter pilot study investigating the use of polymethylmethacrylate for full-face atrophic acne scar correction, 42 adult subjects with a mean age of 43 years were treated and assessed for safety and effectiveness at Months 4 and 7. There were no hypersensitivity reactions to pretreatment skin testing or during scar treatments. RESULTS At 4 and 7 months after initial treatment, 92% and 95% of subjects, respectively, were responders with ≥1-point improvement on the 5-point Acne Scar Assessment Scale. Subjects reported very high levels of improvement on the Global Aesthetic Improvement Scale (GAIS), with 95% of subjects reporting "improved or better" at 4 months and 90% at 7 months. The outcome of the physician GAIS was also high with 92% of patients classified as "improved or better" at 4 months and 97% at 7 months. There were only 2 device-related adverse events, both mild events related to Bellafill skin test (bruising, ecchymosis). There were no serious adverse events in response to the treatment product in this short-term follow-up study. CONCLUSION Polymethylmethacrylate is effective for treating full-face acne scarring. Clinicaltrials.gov #NCT02642627.
NUNS: A Nonuniform Network Split Method for Data-Centric Storage Sensor Networks

If data have the same value frequently in a data-centric storage sensor network, then the load is concentrated on a specific sensor node and the node consumes energy rapidly. In addition, if the sensor network is expanded, the routing distance to the target sensor node becomes longer in data storing and query processing, and this increases the communication cost of the sensor network. This paper proposes a nonuniform network split(NUNS) method that distributes the load among sensor nodes in data-centric storage sensor networks and efficiently reduces the communication cost of expanding sensor networks. NUNS splits a sensor network into partitions of nonuniform sizes in a way of minimizing the difference in the number of sensor nodes and in the size of partitions, and it stores data occurring in each partition in the sensor nodes of the partition. In addition, NUNS splits each partition into zones of nonuniform sizes as many as the number of sensor nodes in the partition in a way of minimizing the difference in the size of the split zones and assigns each zone to the processing area of each sensor node. Finally, we performed various performance evaluations and proved the superiority of NUNS to existing methods.