Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) affects 20%‐40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. ...Electronic medical records facilitate large‐scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases.
Aim
To develop and validate a laboratory parameter‐based machine learning model to detect NAFLD for the general population.
Methods
We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton‐magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver‐operating characteristic curve (AUROC) of models in validation group were compared.
Results
Six predictors including alanine aminotransferase, high‐density lipoprotein cholesterol, triglyceride, haemoglobin A1c, white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83‐0.90) and 0.88 (0.84‐0.91) in the training and validation groups respectively. Using dual cut‐offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%‐96%) sensitivity and 90% (86%‐93%) specificity with corresponding negative and positive predictive values of 96% (91%‐98%) and 69% (59%‐78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate.
Conclusions
NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.
Linked ContentThis article is linked to Gallacher et al and McPherson and Yip papers. To view these articles visit https://doi.org/10.1111/apt.14217 and https://doi.org/10.1111/apt.14234.
The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We ...analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones activating signaling pathways such as FLT3 or RAS or biallelically perturbing TP53. Single-cell studies highlighted the polyclonal nature of intratumoral resistance mechanisms in some cases. Among cases that were primary refractory, we identified heterogeneous and sometimes divergent interval changes in leukemic clones within a single cycle of therapy, highlighting the dynamic and rapid occurrence of therapeutic selection in AML. In functional studies, FLT3 internal tandem duplication gain or TP53 loss conferred cross-resistance to both venetoclax and cytotoxic-based therapies. Collectively, we highlight molecular determinants of outcome with clinical relevance to patients with AML receiving venetoclax-based combination therapies.
•Adaptive resistance is often associated with TP53 abnormalities or kinase activation, particularly FLT3 internal tandem duplication.•NPM1 mutation is associated with excellent survival prospects and durable molecular remission after venetoclax-based combination therapy.
Display omitted
Adolescent idiopathic scoliosis (AIS) disrupts spinal alignment and increases the intrinsic demand for active stabilization to maintain postural stability. Understanding the paraspinal muscle ...fatigability and its effects on spinal alignment and kinematics informs the importance of paraspinal muscle endurance for postural stability. This study aims to investigate the effects of fatigue of thoracic erector spinae on the spinal muscle activity and spinal kinematics in individuals with scoliosis. Spinal muscle activity, posture and mobility measured by electromyography and surface tomography were compared between 15 participants with scoliosis and 15 age- and gender-matched healthy controls during unilateral shoulder flexion and abduction with and without holding a 2-kg weight and performed before and after a fatigue task (prone isometric chest raise). No between-groups difference was found for the spinal extensor endurance. Erector spinae activity at the convex side of AIS group was significantly higher than that at their concave side and than that of healthy controls during shoulder elevations, regardless of the fatigue status. Significant decreases in translational and rotational mobility were found at convex side of AIS group during weighted abduction tasks after fatigue. In contrast, a significant increase in rotational mobility was demonstrated at convex side of AIS participants during weighted flexion tasks after fatigue. Our results revealed a comparable level of spinal extensor endurance between individuals with or without AIS. The increase in muscle activation post-fatigue provides no additional active postural stability but may increase the risk of back pain over the convex side in individuals with scoliosis. Findings highlight imbalances in muscles and the potential implications in optimising neuromuscular activation and endurance capacity in the rehabilitation for AIS patients. Future research is needed to investigate if endurance training of the convex-sided back extensors could optimize the impaired neuromuscular control in the AIS patients.
The histone code refers to the complex network of histone post-translational modifications that control gene expression and are of high interest as drivers of a large number of human diseases. We ...report here on a mix-and-match toolkit of readily available dyes and calixarene host molecules that can be combined to form dye-displacement sensors that respond to a wide variety of cationic peptides. Using the data from only two or three such simple supramolecular sensors as a chemical sensor array produces fingerprints of data that discriminate robustly among many kinds of histone code elements. "Reads" that are accomplished include the discrimination of unmethylated, mono-, di-, and trimethylated lysines on a single histone tail sequence, identification of different modifications and combinations of modifications on a single histone tail sequence, identification of a single modification type in several different sequence contexts, and identification of isomeric dimethylarginine modifications. Reads that are sometimes troublesome for antibodies are achieved. We also report on the ability of the sensor array to report simultaneously on the concentrations and identities of histone modifications. This sensor array discriminates between post-translationally modified analytes without being limited to partners that contain a single, programmed binding interaction.
Small-Diameter Silicon Nanowire Surfaces Ma, D. D. D.; Lee, C. S.; Au, F. C. K. ...
Science (American Association for the Advancement of Science),
03/2003, Letnik:
299, Številka:
5614
Journal Article
Recenzirano
Small-diameter (1 to 7 nanometers) silicon nanowires (SiNWs) were prepared, and their surfaces were removed of oxide and terminated with hydrogen by a hydrofluoric acid dip. Scanning tunneling ...microscopy (STM) of these SiNWs, performed both in air and in ultrahigh vacuum, revealed atomically resolved images that can be interpreted as hydrogen-terminated Si (111)-(1 x 1) and Si (001)-(1 x 1) surfaces corresponding to$SiH_3$on Si (111) and$SiH_2$on Si (001), respectively. These hydrogen-terminated SiNW surfaces seem to be more oxidation-resistant than regular silicon wafer surfaces, because atomically resolved STM images of SiNWs were obtained in air after several days' exposure to the ambient environment. Scanning tunneling spectroscopy measurements were performed on the oxide-removed SiNWs and were used to evaluate the electronic energy gaps. The energy gaps were found to increase with decreasing SiNW diameter from 1.1 electron volts for 7 nanometers to 3.5 electron volts for 1.3 nanometers, in agreement with previous theoretical predictions.
Summary
Background
There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient ...management.
Objectives
The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study.
Methods
Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web‐based survey. The multiple‐response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema.
Results
In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first‐line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second‐line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first‐line antibiotic of choice (78·3%).
Conclusions
In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe.
What's already known about this topic?
There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management.
What does this study add?
The TREAT survey is the first European venture investigating current practice in the use of systemic agents in severe childhood atopic eczema.
The survey confirms significant variability in therapeutic approaches, although there are strong trends favouring a small number of agents, namely ciclosporin, oral corticosteroids and azathioprine.
We present the results of an initial effort to statistically map the fluxes of planetary ions on a closed surface around Mars. Choosing a spherical shell ~1000 km above the planet, we map both ...outgoing and incoming ion fluxes (with energies >25 eV) over a 4 month period. The results show net escape of planetary ions behind Mars and strong fluxes of escaping ions from the northern hemisphere with respect to the solar wind convection electric field. Planetary ions also travel toward the planet, and return fluxes are particularly strong in the southern electric field hemisphere. We obtain a lower bound estimate for planetary ion escape of ~3 × 1024 s−1, accounting for the ~10% of ions that return toward the planet and assuming that the ~70% of the surface covered so far is representative of the regions not yet visited by Mars Atmosphere and Volatile EvolutioN (MAVEN).
Key Points
MAVEN ion measurements are mapped to a spherical surface around Mars
Planetary ion fluxes are organized in four spatial regions on the shell
Heavy ion escape rates exceed 2 × 1024 s−1 for energies >25 eV
An ultrafine-grained (UFG) Al–4Mg–1Zr alloy with a grain size of ∼0.7
μm with predominantly high-angle boundaries of 97% was produced by friction stir processing (FSP). The UFG Al–4Mg–1Zr retained ...submicrometer grains even after static annealing at 425
°C, and exhibited excellent superplasticity at 175–425
°C. High strain rate and low-temperature superplasticity of >1200% were observed at 1
×
10
−2–1
×
10
−1
s
−1 and 300–350
°C. Even at 425
°C, a superplasticity of 1400% was achieved at 1
s
−1. A linear relationship between log
ε
˙
opti and
T was observed (where
ε
˙
opti is the optimum strain rate, and
T is the temperature). The analyses on the superplastic data revealed the presence of threshold stress, a stress exponent of 2, an inverse grain size dependence of 2, and an activation energy of 142
kJ
mol
–1. This indicated that the dominant deformation mechanism was grain boundary sliding, which was controlled by lattice diffusion. Based on this notion, a constitutive equation has been developed. A new superplastic deformation mechanism map for FSP aluminum alloys is proposed.
Graphene (GN) has many beneficial properties that encourage wide applications. Various manufacturing procedures are detailed in the literature but most are unable to produce GN flakes in bulk and ...usually result in toxic discharges. These techniques are also time-consuming and involve operations at high temperatures. A ‘greener’, simpler and a one-step synthesis of the material may be realised by electrochemical oxidation (or reduction) of the graphite host leading to intercalation of ions from the electrolyte (which may be aqueous, organic or an ionic liquid) followed by electrochemical exfoliation. Single- or multi-layered GN flakes can easily be produced in short periods of time, typically within 30min. This paper reviews the state-of-the-art methods reported in the literature regarding electrochemical synthesis of GN flakes as well as their properties (determined via sophisticated analytical methods such as AFM, TEM, SEM or Raman spectroscopy). This is followed by a discussion on the applications of electrochemically prepared GN flakes. Challenges and opportunities are briefly considered leading to the conclusion that the cathodic intercalation of lithium ions into graphite can produce the highest yield (>70%) of pristine GN flakes in organic electrolytes. Future work is recommended with ternary eutectic melts as electrolytes.
Predicting organismal phenotypes from genotype data is important for plant and animal breeding, medicine, and evolutionary biology. Genomic-based phenotype prediction has been applied for ...single-nucleotide polymorphism (SNP) genotyping platforms, but not using complete genome sequences. Here, we report genomic prediction for starvation stress resistance and startle response in Drosophila melanogaster, using ∼2.5 million SNPs determined by sequencing the Drosophila Genetic Reference Panel population of inbred lines. We constructed a genomic relationship matrix from the SNP data and used it in a genomic best linear unbiased prediction (GBLUP) model. We assessed predictive ability as the correlation between predicted genetic values and observed phenotypes by cross-validation, and found a predictive ability of 0.239±0.008 (0.230±0.012) for starvation resistance (startle response). The predictive ability of BayesB, a Bayesian method with internal SNP selection, was not greater than GBLUP. Selection of the 5% SNPs with either the highest absolute effect or variance explained did not improve predictive ability. Predictive ability decreased only when fewer than 150,000 SNPs were used to construct the genomic relationship matrix. We hypothesize that predictive power in this population stems from the SNP-based modeling of the subtle relationship structure caused by long-range linkage disequilibrium and not from population structure or SNPs in linkage disequilibrium with causal variants. We discuss the implications of these results for genomic prediction in other organisms.
PDF
