Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.

BACKGROUND Patients with bronchiectasis have frequent exacerbations that are thought to be related to neutrophilic inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum of patients with bronchiectasis at baseline and increase further during exacerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases. METHODS In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed. RESULTS Of 256 patients, 87 were assigned to receive placebo, 82 to receive 10 mg of brensocatib, and 87 to receive 25 mg of brensocatib. The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group. Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo (P = 0.03 for 10-mg brensocatib vs. placebo; P = 0.04 for 25-mg brensocatib vs. placebo). The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 (95% confidence interval [CI], 0.35 to 0.95) in the 10-mg group (P = 0.03) and 0.62 (95% CI, 0.38 to 0.99) in the 25-mg group (P = 0.046). The incidence-rate ratio was 0.64 (95% CI, 0.42 to 0.98) in the 10-mg group, as compared with placebo (P = 0.04), and 0.75 (95% CI, 0.50 to 1.13) in the 25-mg group, as compared with placebo (P = 0.17). With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo. CONCLUSIONS In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes. (Funded by Insmed; WILLOW ClinicalTrials.gov number, NCT03218917.).
PCR-RFLP Analysis of 12s and 16s Mitochondrial rRNA Genes fromBrackishwater Finfish and Shellfish Species

The use of traditional genetic characterization techniques for detection of genetic variation in aquatic species based on morphological characters has its own limitations. One of the modern approaches to study genetic variation in aquatic species is by Restriction Fragment Length Poly-morphism (RFLP) of mitochondrial DNA (mtDNA). Amplification of mitochondrial 12s and 16s rRNA genes from tiger shrimp ( Penaeus monodon, Penaeidae) , white shrimp ( Fenneropenaeus indicus, Penaeidae), grey mullet ( Mugil cephalus , Mugilidae), tilapia ( Oreochromis mossambicus, Cichlidae), Asian sea bass ( Lates calcarifer , Centropomidae) and mud crabs ( Scylla serrata and Scylla tranquebarica , Portunidae) and the characterization of the amplified PCR products by RFLP have been carried out in the present study. The use of the primers in the present study was found to be universal for amplification of mitochondrial 12s and 16s rRNA genes across the taxo-nomically different brackishwater species examined in this investigation. The amplified products of 12s and 16s rRNA mitochondrial gene segments obtained with these primers can be used for restriction digestion as an approach to obtain species-specific markers by PCR-RFLP analysis.
Antimicrobial Activity of Coriandrum Sativum L. and Its Effect on Microbiological Properties of Yoghurt

In this study, the antimicrobial effect of Coriandrum sativum L. leaves against 30 different foodborne microorganisms, including 20 bacteria, 7 fungi, and 3 yeast species was tested, and some microbiological properties of yoghurt produced with lyophilized C. sativum L. were investigated. Yoghurts were prepared at three different concentrations of C. sativum L. powder (0.1, 0.2, and 0.3% w/w) and stored at 4°C for 21 days. Ethanol extract of the fresh plant showed antimicrobial activity against only 9 bacteria and 1 yeast with different inhibition zone diameter changing from 8 to 12 mm, but had no effect on moulds used in this study. The addition of C. sativum L. had no statistical significance on the growth of yoghurt bacteria compared with the control sample and they remained over 8 log CFU g in all yoghurts throught the storage period. On the other hand, an increase was observed in the number of Lactobacillus bulgaricus and a decrease in the number of Streptococcus thermophilus depending on the concentration of C. sativum L. , but this was not statistically significant (P> 0.05). However, significant differences in yeast and mould counts were observed (P< 0.05). Yeasts and moulds were not detected in any of the samples containing C. sativum L. powder, whereas the counts of yeast and mould increased in control throught the storage period. These results show that the powder of C. sativum L. leaves can be used an agent for preventing the growth of yeast and mould, which are shelf-life and quality spoilage microorganisms of yoghurt.
Changes in physical properties and organic carbon of a Kandiudox fertilized with manure.

Successive applications of pig slurry and poultry manure can improve the soil structure, according to the land use conditions and amounts applied. This study evaluated the effect of manure fertilization on the physical properties and organic carbon of a Rhodic Kandiudox. Treatments included land use and management and time of pig slurry and poultry litter application, namely: native forest (NF); yerba mate after 20 years of animal waste application (YM20); pasture after 15 years of application (P15); grassland after 20 years of manuring (PP20); grassland after 3 years of manuring (P3); pasture without application (P0), maize after 20 years of application (M20); and maize after 7 years of application (M7). Soil samples were collected in the 0-5, 5-10 and 10-20cm layers, in which density, porosity, aggregate stability, flocculation, penetration resistance, available water, and total clay content, total and particulate organic carbon, and C:N ratio were analyzed. The total organic carbon is sensitive to management and was not related to waste application, except in the 10-20cm layer of ryegrass pasture after three years of manuring. Reponses to waste application and land use and management systems were observed in the variables soil density and penetration resistance.
Energetic limits: Defining the bounds and trade‐offs of successful energy management in a capital breeder

Abstract Judicious management of energy can be invaluable for animal survival and reproductive success. Capital breeding mammals typically transfer energy to their young at extremely high rates while undergoing prolonged fasting, making lactation a tremendously energy demanding period. Effective management of the competing demands of the mother's energy needs and those of her offspring is presumably fundamental to maximizing lifetime reproductive success. How does the mother maximize her chances of successfully rearing her pup, by ensuring that both her pup and herself have sufficient energy during this ‘energetic fast’? While energy management models were first discussed in the 1990s, application of this analytical technique is still very much in its infancy. Recent work suggests that a broad range of species exhibits ‘energy compensation’; during periods when they expend more energy on activity, their bodies partially compensate by reducing background (basal) metabolic rate as an adaptation to limit overall energy expenditure. However, the value of energy management models in understanding animal ecology is presently unclear. We investigate whether energy management models provide insights into the breeding strategy of phocid seals. Not only do we expect lactating seals to display energy compensation because of their breeding strategy of high energy transfer while fasting, but we anticipate that mothers exhibiting a lack of energy compensation are less likely to rear offspring successfully. On the Isle of May in Scotland, we collected heart rate data as a proxy for energy expenditure in 52 known individual grey seal (Halichoerus grypus) mothers, repeatedly across 3 years of breeding. We provide evidence that grey seal mothers typically exhibit energy compensation during lactation by downregulating their background metabolic rate to limit daily energy expenditure during periods when other energy costs are relatively high. However, individuals that fail to energy compensate during the lactation period are more likely to end lactation earlier than expected. Our study is the first to demonstrate the importance of energy compensation to an animal's reproductive expenditure. Moreover, our multi‐seasonal data indicate that environmental stressors may reduce the capacity of some individuals to follow the energy compensation strategy.
Electrophysiological sign of stronger auditory processing in females than males during passive listening

ABSTRACT Available literature shows sex-related differences in both anatomy and functions of the auditory cortex. However, only few data are available on passive listening. By means of event-related potentials (ERPs), we analyzed the proactive and reactive stages of processing related to passive listening in 36 healthy young participants, equally balanced between genders. The anterior positivity (aP), a newly discovered pre-stimulus component originating in auditory cortices and indexing auditory readiness, was not different between genders; the post-stimulus components (the N1 and the N2, originating in primary and secondary auditory cortices) were larger in females than males. These results not only provide significant insights on sex-related differences during listening, but also encourage the potential use of passive tasks, which allow for better understanding of basic neural processing, without interferences from cognitive requirements of active tasks.
ANALYSIS OF CODON USAGE IN MAIZE

It's widespread existence of codon usage bias in organism which has an important influence for expression intensity of exogenous gene.In this study,coding sequences of 7402 proteins were analyzed by CodonW and CUSP programs in maize genome,calculating frequency of codon usage which encoded amino acids and comparing with variety classes of mode organisms such as:human being,yeast,E.coli,Drosophila.These results had shown that codon bias of maize was difference in various degrees with these mode organisms.Comparing codon usage frequency of maize with dicotyledons and monocotyledons including Arabidopsis thaliana,tobacco,rice,wheat,the consequence indicated that codon usage frequency of maize was obviously different from Arabidopsis thaliana and tobacco which belonged to dicotyledon,but had a consistency with codon bias of rice and wheat which are monocotyl.These analytic results had important guidance for maize gene-transforming and selecting the high-efficient expression system.
Equivalent performance of single-use and reusable duodenoscopes in a randomised trial

Objective Single-use duodenoscopes have been recently developed to eliminate risk of infection transmission from contaminated reusable duodenoscopes. We compared performances of single-use and reusable duodenoscopes in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Design Patients with native papilla requiring ERCP were randomised to single-use or reusable duodenoscope. Primary outcome was comparing number of attempts to achieve successful cannulation of desired duct. Secondary outcomes were technical performance that measured duodenoscope manoeuvrability, mechanical-imaging characteristics and ability to perform therapeutic interventions, need for advanced cannulation techniques or cross-over to alternate duodenoscope group to achieve ductal access and adverse events. Results 98 patients were treated using single-use (n=48) or reusable (n=50) duodenoscopes with >80% graded as low-complexity procedures. While median number of attempts to achieve successful cannulation was significantly lower for single-use cohort (2 vs 5, p=0.013), ease of passage into stomach (p=0.047), image quality (p<0.001), image stability (p<0.001) and air–water button functionality (p<0.001) were significantly worse. There was no significant difference in rate of cannulation, adverse events including mortality (one patient in each group), need to cross-over or need for advanced cannulation techniques to achieve ductal access, between cohorts. On multivariate logistic regression analysis, only duodenoscope type (single-use) was associated with less than six attempts to achieve selective cannulation (p=0.012), when adjusted for patient demographics, procedural complexity and type of intervention. Conclusion Given the overall safety profile and similar technical performance, single-use duodenoscopes represent an alternative to reusable duodenoscopes for performing low-complexity ERCP procedures in experienced hands. Trial registration number Clinicaltrials.gov number: NCT04143698
Leveraging Immonium Ions for Targeting Acyl‐Lysine Modifications in Proteomic Datasets

Acyl modifications vary greatly in terms of elemental composition and site of protein modification. Developing methods to identify acyl modifications more confidently can help to assess the scope of these modifications in large proteomic datasets. The utility of acyl‐lysine immonium ions is analyzed for identifying the modifications in proteomic datasets. It is demonstrated that the cyclized immonium ion is a strong indicator of acyl‐lysine presence when its rank or relative abundance compared to other ions within a spectrum is considered. Utilizing a stepped collision energy method in a shotgun experiment highlights the immonium ion. By implementing an analysis that accounted for features within each MS2 spectrum, the method clearly identifies peptides with short chain acyl‐lysine modifications from complex lysates. Immonium ions can also be used to validate novel acyl modifications; in this study, the first examples of 3‐hydroxylpimelyl‐lysine modifications are reported and they are validated using immonium ions. Overall these results solidify the use of the immonium ion as a marker for acyl‐lysine modifications in complex proteomic datasets.
An overview of the key principles and guidelines in the management of pelvic fractures

Pelvic fractures are complex injuries with a range of different presentations depending on the mechanism of trauma. Due to the morbidity and mortality of pelvic fractures, patients require thorough investigation and timely management with multidisciplinary input. Various surgical and non-surgical techniques can be used to treat pelvic fractures, as well as any associated visceral injuries. Following repair, it is important to remain vigilant for postoperative complications such as infection, sexual and urinary dysfunction, chronic pain and adverse psychological health. This article summarises the relevant UK guidance and literature and presents them in a format that follows the patient’s journey. In doing so, it highlights the key perioperative factors that need to be considered in cases of pelvic fracture.
Computational framework for detection of subtypes of neuropsychiatric disorders based on DTI-derived anatomical connectivity

Many brain disorders – such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and autism – are heterogeneous, that is, they may have several subtypes. Traditionally, clinicians have identified subtypes, such as subtypes of psychosis, using clinical criteria. Neuroimaging has the potential to detect subtypes based on objective biomarker-based criteria; however, there are no studies that evaluate the application of combining unsupervised machine learning and anatomical connectivity analysis to accomplish this goal. We propose a computational framework to detect subtypes based on anatomical connectivity computed from diffusion tensor imaging data, in a data-driven and fully automated way. The proposed method exhibits excellent performance on simulated data. We also applied this approach to a real-world dataset: the Nathan Kline Institute data set. The Nathan Kline Institute study consists of 137 normal adult subjects (mean age 41 years (standard deviation 18), male/female 85/52). We examined the association between detected subtypes and the impulsive behavior scale. We found that a subtype characterized by lower connectivity scores was associated with a higher positive urgency score; positive urgency is a vulnerability marker for drug addiction. The top-ranked connections characterizing subtypes involve several brain regions, including the anterior cingulate gyrus, median cingulate gyrus, thalamus, superior frontal gyrus (medial), middle frontal gyrus (orbital part), inferior frontal gyrus (triangular part), superior frontal gyrus, precuneus and putamen. The proposed framework is extendable, and can be used to detect subtypes from other features, including clinical and genomic biomarkers.
Quantitative Sensory Testing Protocols to Evaluate Central and Peripheral Sensitization in Knee OA: A Protocol for a Scoping Review.

BACKGROUND Quantitative sensory testing (QST) methods have become widely used for the assessment of nervous system sensitization to nociceptive signalling in studies of people with knee osteoarthritis (OA). However, few standardised QST protocols have been developed. Variability in their execution may lead to differences in their interpretation. OBJECTIVE The proposed scoping review will seek to identify the various QST methodologies being used in the assessment of sensitization and how sensitization is being defined in people with knee OA. Methods and Analysis: This scoping review will be guided by existing scoping review methodologies. Relevant studies will be extracted from the following electronic databases: Medical Literature Analysis and Retrieval System Online, ExcerptaMedica Database, Allied and Complementary Medicine Database and the Cumulative Index to Nursing Allied Health Literature. Independent screening of the abstracts and full articles and data extraction will be performed in pairs. Information extracted will focus on qualitative and quantitative data relevant to the content of the protocols from included studies. Data will be summarised in order to draw conclusions on the common elements used in QST protocols and definitions of sensitization for knee OA. CONCLUSION This scoping review will provide insight into the most common methods of QST being implemented in the assessment of nervous system sensitization to nociceptive signalling in people with knee OA. This will potentially identify areas where a systematic review or other primary research may be required in order to develop fixed evidence-based protocols for QST in patients with knee OA.
A Novel Method for Constructing Classification Models by Combining Different Biomarker Patterns

Different biomarker patterns, such as those of molecular biomarkers and ratio biomarkers, have their own merits in clinical applications. In this study, a novel machine learning method used in biomedical data analysis for constructing classification models by combining different biomarker patterns (CDBP)is proposed. CDBP uses relative expression reversals to measure the discriminative ability of different biomarker patterns, and selects the pattern with the higher score for classifier construction. The decision boundary of CDBP can be characterized in simple and biologically meaningful manners. The CDBP method was compared with eight state-of-the-art methods on eight gene expression datasets to test its performance. CDBP, with fewer features or ratio features, had the highest classification performance. Subsequently, CDBP was employed to extract crucial diagnostic information from a rat hepatocarcinogenesis metabolomics dataset. The potential biomarkers selected by CDBP provided better classification of hepatocellular carcinoma (HCC)and non-HCC stages than previous works in the animal model. The statistical analyses of these potential biomarkers in an independent human dataset confirmed their discriminative abilities of different liver diseases. These experimental results highlight the potential of CDBP for biomarker identification from high-dimensional biomedical datasets and demonstrate that it can be a useful tool for disease classification.
The emergence and spillover of bumblebee parasites

Pollinators and in particular, bumblebees are currently experiencing significant declines. In Britain, bumblebee populations have been declining since the industrial revolution. Modern farming now requires large, monoculture fields to be effectively pollinated, yet the very nature of such large, homogeneous environments prevents many wild pollinators to thrive there. Since the mid-1980s bumblebees have been reared and imported on an industrial scale to aid the pollination of many valuable crops such as tomatoes and raspberry. There is great concern that the intensive rearing and importation of these bumblebees may permit the introduction of exotic parasites to native bumblebees. These concerns follow suggestions that parasite spillover from commercially reared bumblebees may be occurring; with declines of wild bumblebees in North and South America correlated with commercial bumblebee use. It’s believed that around 50, 000 bumblebee hives are imported into the UK every year and whilst they are purported to be disease free, no independent testing is carried out. Here, I assess what risk the use of commercial bumblebees has on native bees. By screening commercially reared and imported bumblebee colonies for a range of bumblebee and honey bee parasites, I identified the majority have infections. The parasites detected include the emerging diseases Apicystis bombi and Nosema ceranae which are found to be lethal to infected bumblebees. Shared flowers between bumblebees and honey bees are shown to be platforms for the dispersal of many of these parasites. The frequent mixing between domesticated and wild bumblebees allows potential transmission of these parasites. The deployment of commercial bumblebees was shown to increase parasite prevalence within local populations of wild bumblebees and when bumblebees have increased competition in the form of domesticated honey bees, they once again have higher parasite prevalence. Here I show that not only are current import regulation inadequate to avoid introducing infected bumblebees into England, but that there are clear opportunities and evidence that transmission is occurring.