Miracle-dz/UniFAR-FTUs huggingface dataset:
The application of 595-nm pulsed dye laser for vascular anomalies in a Chinese population: a 10-year experience

ABSTRACT Background: The 595-nm pulsed dye laser (PDL) has been used to treat vascular anomalies for about 30 years; however, there are insufficient data in Chinese patients concerning therapeutic efficacy, optimized parameters, and procedure techniques. Objective: To study the efficacy and relevant factors in PDL therapy for vascular anomalies in Chinese patients. Method: We enrolled 431 patients with 8 different vascular anomalies and no previous treatment in this retrospective study. A detailed classification of vascular anomalies and various parameters and techniques of PDL were studied. The clinical outcomes were analysed using the Investigator Global Assessment. Results: Improvements were significantly correlated with infantile haemangioma (IH) subtypes (p < 0.05). A significant correlation between efficacy and lesion colour, anatomical sites, and hypertrophic-type port-wine stain (PWS) was found (p < 0.05). There was no significant correlation between efficacy and age or sex (p > 0.05). Conclusion: PDL is an effective and safe therapeutic modality for managing vascular anomalies in Chinese patients. We determined that differentiating and identifying IH subtypes prior to treatment could be a useful parameter for predicting therapeutic results. Lesion colour, sites, and hypertrophic changes in PWS are relevant therapeutic factors. PDL parameters and techniques differ according to the various vascular anomalies to achieve optimal results.
Opening the black box of diagnosis-related groups (DRGs): unpacking the technical remuneration structure of the Dutch DRG system

Abstract While we know that upcoding of diagnosis-related groups (DRGs) regularly occurs, we have little knowledge of the role of the technical features of coding systems in inducing coding behaviour. This paper presents methods for investigating the financial structure of the Dutch DRG system, and more in particular the grouper software, to gain such insight. The paper describes a system for investigating the robustness of the reward structure, by simulating the response of the DRG system to small changes in individual coding. The results from these analyses are used to visualise some data on coding behaviour, and to investigate how this behaviour is affected by incentives in the technical features of the DRG system. A number of technical weaknesses in the system are also identified.
Information content of cluster–period cells in stepped wedge trials

Stepped wedge and other multiple‐period cluster randomized trials, which collect data from multiple clusters across multiple time periods, are being conducted with increasing frequency; statistical research into these designs has not kept apace. In particular, some stepped wedge designs with missing cluster–period “cells” have been proposed without any formal justification. Indeed there are no general guidelines regarding which cells of a stepped wedge design contribute the least information toward estimation of the treatment effect, and correspondingly which may be preferentially omitted. In this article, we define a metric of the information content of cluster–period cells, entire treatment sequences, and entire periods of the standard stepped wedge design as the increase in variance of the estimator of the treatment effect when that cell, sequence, or period is omitted. We show that the most information‐rich cells are those that occur immediately before or after treatment switches, but also that there are additional cells that contribute almost as much to the estimation of the treatment effect. However, the information content patterns depend on the assumed correlation structure for the repeated measurements within a cluster.
Effectiveness of Scaled Exponentially-Regularized Linear Units (SERLUs)

Recently, self-normalizing neural networks (SNNs) have been proposed with the intention to avoid batch or weight normalization. The key step in SNNs is to properly scale the exponential linear unit (referred to as SELU) to inherently incorporate normalization based on central limit theory. SELU is a monotonically increasing function, where it has an approximately constant negative output for large negative input. In this work, we propose a new activation function to break the monotonicity property of SELU while still preserving the self-normalizing property. Differently from SELU, the new function introduces a bump-shaped function in the region of negative input by regularizing a linear function with a scaled exponential function, which is referred to as a scaled exponentially-regularized linear unit (SERLU). The bump-shaped function has approximately zero response to large negative input while being able to push the output of SERLU towards zero mean statistically. To effectively combat over-fitting, we develop a so-called shift-dropout for SERLU, which includes standard dropout as a special case. Experimental results on MNIST, CIFAR10 and CIFAR100 show that SERLU-based neural networks provide consistently promising results in comparison to other 5 activation functions including ELU, SELU, Swish, Leakly ReLU and ReLU.
Induction of Oxidative DNA Damage in Bovine Herpesvirus 1 Infected Bovine Kidney Cells (MDBK Cells) and Human Tumor Cells (A549 Cells and U2OS Cells)

Bovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle that causes lesions in mucosal surfaces, genital tracts and nervous systems. As a novel oncolytic virus, BoHV-1 infects and kills numerous human tumor cells. However, the mechanisms underlying the virus-induced cell damages are not fully understood. In this study, we demonstrated that virus infection of MDBK cells induced high levels of DNA damage, because the percentage of comet tail DNA (tailDNA%) determined by comet assay, a direct indicator of DNA damage, and the levels of 8-hydroxyguanine (8-oxoG) production, an oxidative DNA damage marker, consistently increased following the virus infection. The expression of 8-oxoguanine DNA glycosylase (OGG-1), an enzyme responsible for the excision of 8-oxoG, was significantly decreased due to the virus infection, which corroborated with the finding that BoHV-1 infection stimulated 8-oxoG production. Furthermore, the virus replication in human tumor cells such as in A549 cells and U2OS cells also induced DNA damage. Chemical inhibition of reactive oxidative species (ROS) production by either ROS scavenger N-Acetyl-l-cysteine or NOX inhibitor diphenylene iodonium (DPI) significantly decreased the levels of tailDNA%, suggesting the involvement of ROS in the virus induced DNA lesions. Collectively, these results indicated that BoHV-1 infection of these cells elicits oxidative DNA damages, providing a perspective in understanding the mechanisms by which the virus induces cell death in both native host cells and human tumor cells.
A simplified curcumin targets the membrane of Bacillus subtilis

Curcumin is the main constituent of turmeric, a seasoning popularized around the world with Indian cuisine. Among the benefits attributed to curcumin are anti‐inflammatory, antimicrobial, antitumoral, and chemopreventive effects. Besides, curcumin inhibits the growth of the gram‐positive bacterium Bacillus subtilis. The anti‐B. subtilis action happens by interference with the division protein FtsZ, an ancestral tubulin widespread in Bacteria. FtsZ forms protofilaments in a GTP‐dependent manner, with the concomitant recruitment of essential factors to operate cell division. By stimulating the GTPase activity of FtsZ, curcumin destabilizes its function. Recently, curcumin was shown to promote membrane permeabilization in B. subtilis. Here, we used molecular simplification to dissect the functionalities of curcumin. A simplified form, in which a monocarbonyl group substituted the β‐diketone moiety, showed antibacterial action against gram‐positive and gram‐negative bacteria of clinical interest. The simplified curcumin also disrupted the divisional septum of B. subtilis; however, subsequent biochemical analysis did not support a direct action on FtsZ. Our results suggest that the simplified curcumin exerted its function mainly through membrane permeabilization, with disruption of the membrane potential necessary for FtsZ intra‐cellular localization. Finally, we show here experimental evidence for the requirement of the β‐diketone group of curcumin for its interaction with FtsZ.
Heritability and genome-wide association study of diffusing capacity of the lung

Although several genome-wide association studies (GWAS) have investigated the genetics of pulmonary ventilatory function, little is known about the genetic factors that influence gas exchange. The aim of the study was to investigate the heritability of, and genetic variants associated with the diffusing capacity of the lung. GWAS was performed on diffusing capacity of the lung measured by carbon monoxide uptake (DLCO) and per alveolar volume (VA) using the single-breath technique, in 8372 individuals from two population-based cohort studies, the Rotterdam Study and the Framingham Heart Study. Heritability was estimated in related (n=6246) and unrelated (n=3286) individuals. Heritability of DLCO and DLCO/VA ranged between 23% and 28% in unrelated individuals and between 45% and 49% in related individuals. Meta-analysis identified a genetic variant in ADGRG6 that is significantly associated with DLCO/VA. Gene expression analysis of ADGRG6 in human lung tissue revealed a decreased expression in patients with chronic obstructive pulmonary disease (COPD) and subjects with decreased DLCO/VA. DLCO and DLCO/VA are heritable traits, with a considerable proportion of variance explained by genetics. A functional variant in ADGRG6 gene region was significantly associated with DLCO/VA. Pulmonary ADGRG6 expression was decreased in patients with COPD. This is the first population-based heritability and GWAS study of gas exchange. We identified a functional variant in ADGRG6, and demonstrated differential expression in lung tissue of patients with COPD and decreased diffusing capacity. http://ow.ly/Rvy430kHIT4
Urea and creatinine detection on nano-laminated gold thin film using Kretschmann-based surface plasmon resonance biosensor

This work investigates the surface plasmon resonance (SPR) response of 50-nm thick nano-laminated gold film using Kretschmann-based biosensing for detection of urea and creatinine in solution of various concentrations (non-enzymatic samples). Comparison was made with the presence of urease and creatininase enzymes in the urea and creatinine solutions (enzymatic samples), respectively. Angular interrogation technique was applied using optical wavelengths of 670 nm and 785 nm. The biosensor detects the presence of urea and creatinine at concentrations ranging from 50–800 mM for urea samples and 10–200 mM for creatinine samples. The purpose of studying the enzymatic sample was mainly to enhance the sensitivity of the sensor towards urea and creatinine in the samples. Upon exposure to 670 nm optical wavelength, the sensitivity of 1.4°/M was detected in non-enzymatic urea samples and 4°/M in non-enzymatic creatinine samples. On the other hand, sensor sensitivity as high as 16.2°/M in urea-urease samples and 10°/M in creatinine-creatininase samples was detected. The enhanced sensitivity possibly attributed to the increase in refractive index of analyte sensing layer due to urea-urease and creatinine-creatininase coupling activity. This work has successfully proved the design and demonstrated a proof-of-concept experiment using a low-cost and easy fabrication of Kretschmann based nano-laminated gold film SPR biosensor for detection of urea and creatinine using urease and creatininase enzymes.
Executive Functioning Mediates the Relationship Between Pain Coping and Quality of Life in Youth With Sickle Cell Disease

Objective Sickle cell disease (SCD) is a lifelong condition characterized by pain, which is associated with reduced health-related quality of life (HRQL). Data suggest that patients with SCD vary in how they cope and their neurocognitive abilities. This study aimed to characterize executive functioning and pain coping styles in children with SCD experiencing a range of pain frequency (i.e., chronic, episodic, and asymptomatic) and to examine whether executive functioning mediates the relationship between pain coping and HRQL. Method Participants included 100 children and adolescents with SCD between the ages of 8 and 18 years (M = 13.53, SD = 2.8) and their parents who were recruited during outpatient SCD clinic visits in a children's hospital. Children completed questionnaires related to pain experience and pain coping. Parents completed questionnaires about demographic information, their child's executive functioning, and HRQL. Results Pain intensity, executive dysfunction, and engagement in emotion-focused coping (i.e., internalizing/catastrophizing and externalizing) predicted poor HRQL. In addition, engagement in emotion-focused coping predicted executive dysfunction. Multivariate analysis of covariance revealed executive functioning did not differ based on pain frequency; however, executive functioning was a significant mediator that helped explain the relationships between distraction and emotion-focused coping techniques on HRQL. Conclusion Findings support that executive functioning is an important factor in understanding the relationship between pain coping and HRQL in youth with SCD. Future research is warranted to examine the potential impact of executive functioning on the utility of interventions targeting adaptive pain coping in youth with SCD.
WebMetabase: cleavage sites analysis tool for natural and unnatural substrates from diverse data source

Summary: More than 150 peptide therapeutics are globally in clinical development. Many enzymatic barriers should be crossed by a successful drug to be prosperous in such a process. Therefore, the new peptide drugs must be designed preventing the potential protease cleavage to make the compound less susceptible to protease reaction. We present a new data analysis tool developed in WebMetabase, an approach that stores the information from liquid chromatography mass spectrometry‐based experimental data or from external sources such as the MEROPS database. The tool is a chemically aware system where each peptide substrate is presented as a sequence of structural blocks (SBs) connected by amide bonds and not being limited to the natural amino acids. Each SB is characterized by its pharmacophoric and physicochemical properties including a similarity score that describes likelihood between a SB and each one of the other SBs in the database. This methodology can be used to perform a frequency analysis to discover the most frequent cleavage sites for similar amide bonds, defined based on the similarity of the SB that participate in such a bond within the experimentally derived and/or public database. Availability and implementation: http://webmetabase.com:8182/WebMetabaseBioinformatics/ Supplementary information: Supplementary data are available at Bioinformatics online.
gMCS: fast computation of genetic minimal cut sets in large networks

Motivation The identification of minimal gene knockout strategies to engineer metabolic systems constitutes one of the most relevant applications of the COnstraint‐Based Reconstruction and Analysis (COBRA) framework. In the last years, the minimal cut sets (MCSs) approach has emerged as a promising tool to carry out this task. However, MCSs define reaction knockout strategies, which are not necessarily transformed into feasible strategies at the gene level. Results We present a more general, easy‐to‐use and efficient computational implementation of a previously published algorithm to calculate MCSs to the gene level (gMCSs). Our tool was compared with existing methods in order to calculate essential genes and synthetic lethals in metabolic networks of different complexity, showing a significant reduction in model size and computation time. Availability and implementation gMCS is publicly and freely available under GNU license in the COBRA toolbox (https://github.com/opencobra/cobratoolbox/tree/master/src/analysis/gMCS). Supplementary information Supplementary data are available at Bioinformatics online.
Novel mosaic SRY gene deletions in three newborn males with variable genitourinary malformations

Ambiguous genitalia in the newborn can present a diagnostic challenge in medical practice. In most cases, the causes of genitourinary anomalies are not well understood; both genetic and environmental factors are thought to play a role. In this study, we report mosaic SRY gene deletion identified by fluorescence in situ hybridization (FISH) analysis in three unrelated newborn male patients with genital anomalies. G‐banded chromosomes and microarray analysis were normal for all three patients. One patient had microphallus, hypospadias, bifid scrotum, exstrophic perineal tissue identified as a rectal duplication, lumbar vertebral anomalies, scoliosis, and a dysmorphic sacrum. The other two patients had isolated epispadias with the urethral meatus close to the penopubic junction. All three had bilateral palpable gonads in the scrotum. While this is the first report of mosaic SRY deletions, mosaic SRY sequence variants have been described in patients with variable genitourinary anomalies. This study identifies FISH analysis as a reliable method for mosaic SRY deletion detection. We suggest SRY FISH analysis should be used in the clinical workup of patients with genitourinary ambiguity.
Characterisation of the Brochothrix thermosphacta sortase A enzyme

Gram-positive bacteria utilise class A sortases to coat the surface of their cells with a diversity of proteins that facilitate interactions with their environment and play fundamental roles in cell physiology and virulence. A putative sortase A gene was identified in the genome of the poorly studied meat spoilage bacterium Brochothrix thermosphacta. To understand how this bacterium mediates interactions with its environment, an N-terminal truncated, His-tagged variant of this protein (His6-BtSrtA) was expressed and purified. Catalytic activity of recombinant His6-BtSrtA was investigated, including sorting motif recognition of target proteins and bioconjugation activity. Further, the B. thermosphacta genome was examined for the presence of sortase A (SrtA) protein substrates. His6-BtSrtA readily formed intermediate complexes with LPXTG-tagged proteins. Although the reaction was inefficient, nucleophilic attack of the resultant thioacyl intermediates by tri-glycine was observed. Genome examination identified 11 potential SrtA substrates, two of which contained protein domains associated with adherence of pathogens to host extracellular matrix proteins and cells, suggesting the B. thermosphacta SrtA may be indirectly involved in its attachment to meat surfaces. Thus, further work in this area could provide crucial insight into molecular mechanisms involved in the colonisation of meat by B. thermosphacta.
Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptor β2 Agonist

Vitamin A (VA) and its derivatives, known as retinoids, play critical roles in renal development through retinoic acid receptor β2 (RARβ2). Disruptions in VA signaling pathways are associated with the onset of diabetic nephropathy (DN). Despite the known role of RARβ2 in renal development, the effects of selective agonists for RARβ2 in a high-fat diet (HFD) model of DN are unknown. Here we examined whether AC261066 (AC261), a highly selective agonist for RARβ2, exhibited therapeutic effects in a HFD model of DN in C57BL/6 mice. Twelve weeks of AC261 administration to HFD-fed mice was well tolerated with no observable side effects. Compared with HFD-fed mice, HFD + AC261–treated mice had improved glycemic control and reductions in proteinuria and urine albumin-to-creatinine ratio. Several cellular hallmarks of DN were mitigated in HFD + AC261–treated mice, including reductions in tubule lipid droplets, podocyte (POD) effacement, endothelial cell collapse, mesangial expansion, and glomerular basement membrane thickening. Mesangial and tubule interstitial expression of the myofibroblast markers α-smooth muscle actin (α-SMA) and type IV collagen (Col-IV) was lower in HFD + AC261–treated mice compared with HFD alone. Ultrastructural and immunohistochemistry analyses showed that, compared with HFD-fed mice, HFD + AC261–treated mice showed preservation of POD foot process and slit-diaphragm morphology, an increase in the levels of slit-diagram protein podocin, and the transcription factor Wilms tumor-suppressor gene 1 in PODs. Given the need for novel DN therapies, our results warrant further studies of the therapeutic properties of AC261 in DN.
Effects of daily inspiratory muscle training on respiratory muscle strength and chest wall regional volumes in haemodialysis patients: a randomised clinical trial

Abstract Purpose: Evaluating the effects of interdialytic daily inspiratory muscle training (IMT) on respiratory muscle strength, chest wall regional volumes, diaphragmatic mobility and thickness, pulmonary function, functional capacity, and quality of life (QoL) in haemodialysis (HD) patients. Method: A randomised, and double-blind clinical trial composed of 24 chronic kidney disease patients undergoing HD. Patients were allocated into the IMT group (n = 12) or sham group (n = 12) and performed daily IMT twice per day with a load of 50% inspiratory muscle strength for the IMT group and 5 cmH2O for the sham group during 8 weeks. Respiratory muscle strength, diaphragm thickness and mobility, chest wall regional volumes, functional capacity, and QoL were measured. Results: At the end of the study, an increase in inspiratory and expiratory muscle strength was observed for both groups, but no significant difference was found between them. Changed volume distribution was also observed in the IMT group, with significantly increased inspiratory capacity in the pulmonary compartment compared to the sham group. Conclusions: Daily interdialytic IMT promoted a change in chest wall regional volumes, with an increase in the inspiratory capacity of the pulmonary rib cage. Both groups had increased inspiratory and expiratory muscle strength with daily respiratory exercise.Trial registration: www.ClinicalTrials. gov; study number: NCT02599987; name of trial registry: IMT in Patients with End-stage Renal Disease. Implications for rehabilitation Muscular impairment in chronic kidney disease patients results from a series of common alterations, affecting respiratory muscles. Patients with chronic kidney disease have low values of diaphragmatic thickness. The daily inspiratory muscle training (IMT) or breathing exercise over a period of 8 weeks provided increased respiratory muscle strength. The daily inspiratory muscle training presented a change in tri-compartment distribution of lung volume compared to the sham group, with increased inspiratory capacity of the pulmonary rib cage.
The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle‐aged women is not caused by leucine alone

It has been suggested that leucine is primarily responsible for the increase in muscle protein synthesis after protein ingestion because leucine uniquely activates the mTOR‐p70S6K signalling cascade. We compared the effects of ingesting protein or an amount of leucine equal to that in the protein during a hyperinsulinaemic‐euglycaemic clamp (to eliminate potential confounding as a result of differences in the insulinogenic effect of protein and leucine ingestion) on muscle anabolic signalling and protein turnover in 28 women. We found that protein, but not leucine, ingestion increased muscle p‐mTORSer2448 and p‐p70S6KThr389, although only protein, and not leucine, ingestion decreased muscle p‐eIF2αSer51 and increased muscle protein synthesis.