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.
MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid ...leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.
Abstract Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar disorder, and have been shown to have neuroprotective properties in vivo and in vitro . A recent study ...demonstrated that combined treatment with lithium and VPA elicits synergistic neuroprotective effects against glutamate excitotoxicity in cultured brain neurons, and the synergy involves potentiated inhibition of glycogen synthase kinase-3 (GSK-3) activity through enhanced GSK-3 serine phosphorylation Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM (2008) Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J Neurosci 28:2576–2588. We therefore investigated the effects of lithium and VPA cotreatment on the disease symptom onset, survival time and neurological deficits in cooper zinc superoxide dismutase (SOD1) G93A mutant mice, a commonly used mouse model of amyotrophic lateral sclerosis (ALS). The G93A ALS mice received twice daily i.p. injections with LiCl (60 mg/kg), VPA (300 mg/kg) or lithium plus VPA, starting from the 30th day after birth and continuing until death. We found that combined treatment with lithium and VPA produced a greater and more consistent effect in delaying the onset of disease symptoms, prolonging the lifespan and decreasing the neurological deficit scores, compared with the results of monotreatment with lithium or VPA. Moreover, lithium in conjunction with VPA was more effective than lithium or VPA alone in enhancing the immunostaining of phospho-GSK-3βSer9 in brain and lumbar spinal cord sections. To our knowledge, this is the first demonstration of enhanced neuroprotection by a combinatorial approach using mood stabilizers in a mouse ALS model. Our results suggest that clinical trials using lithium and VPA in combination for ALS patients are a rational strategy.
This paper reports world averages of measurements of
b
-hadron,
c
-hadron, and
τ
-lepton properties obtained by the Heavy Flavour Averaging Group using results available through September 2018. In ...rare cases, significant results obtained several months later are also used. For the averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters,
C
P
violation parameters, parameters of semileptonic decays, and Cabibbo–Kobayashi–Maskawa matrix elements.
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature ...is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype‐guided warfarin dosing to achieve a target international normalized ratio of 2–3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at ...Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.
Graphene and other two-dimensional (2D) materials have emerged as promising materials for broadband and ultrafast photodetection and optical modulation. These optoelectronic capabilities can augment ...complementary metal–oxide–semiconductor (CMOS) devices for high-speed and low-power optical interconnects. Here, we demonstrate an on-chip ultrafast photodetector based on a two-dimensional heterostructure consisting of high-quality graphene encapsulated in hexagonal boron nitride. Coupled to the optical mode of a silicon waveguide, this 2D heterostructure-based photodetector exhibits a maximum responsivity of 0.36 A/W and high-speed operation with a 3 dB cutoff at 42 GHz. From photocurrent measurements as a function of the top-gate and source-drain voltages, we conclude that the photoresponse is consistent with hot electron mediated effects. At moderate peak powers above 50 mW, we observe a saturating photocurrent consistent with the mechanisms of electron–phonon supercollision cooling. This nonlinear photoresponse enables optical on-chip autocorrelation measurements with picosecond-scale timing resolution and exceptionally low peak powers.
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