There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma.
We measured ...relative abundance of
(
),
(
) and
(
) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects.
The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker
in patients with advanced adenoma than controls (p=0.022). The marker
, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively).
This study identified marker
as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.
Aims/hypothesis
Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the ...aim of identifying novel variants for type 2 diabetes in Asians.
Methods
We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.
Results
We identified
CDKN2A/B
and four novel type 2 diabetes association signals with
p
< 1 × 10
−5
from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (
p
meta
= 2.6 × 10
−8
; OR 95% CI 1.18 1.11, 1.25). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (
p
meta
= 2.3 × 10
−10
) and a population of European descent (
p
= 8.6 × 10
−3
). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.
Conclusions/interpretation
Our study identifies rs10229583 near
PAX4
as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.
Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker ...of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.
Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)
; however, most of these loci have been identified in ...analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells
. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues
. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.
To investigate the global incidence of prostate cancer with special attention to the changing age structures. Data regarding the cancer incidence and population statistics were retrieved from the ...International Agency for Research on Cancer in World Health Organization. Eight developing and developed jurisdictions in Asia and the Western countries were selected for global comparison. Time series were constructed based on the cancer incidence rates from 1988 to 2007. The incidence rate of the population aged ≥ 65 was adjusted by the increasing proportion of elderly population, and was defined as the "aging-adjusted incidence rate". Cancer incidence and population were then projected to 2030. The aging-adjusted incidence rates of prostate cancer in Asia (Hong Kong, Japan and China) and the developing Western countries (Costa Rica and Croatia) had increased progressively with time. In the developed Western countries (the United States, the United Kingdom and Sweden), we observed initial increases in the aging-adjusted incidence rates of prostate cancer, which then gradually plateaued and even decreased with time. Projections showed that the aging-adjusted incidence rates of prostate cancer in Asia and the developing Western countries were expected to increase in much larger extents than the developed Western countries.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
c-Met represents an important emerging therapeutic target in cancer. In this study, we demonstrate the mechanism by which c-Met tyrosine kinase inhibition inhibits tumor growth in a highly invasive ...Asian-prevalent head and neck cancer, nasopharyngeal cancer (NPC). c-Met tyrosine kinase inhibitors (TKIs; AM7 and c-Met TKI tool compound SU11274) downregulated c-Met phosphorylation, resulting in marked inhibition of NPC cell growth and invasion. Strikingly, inhibition of c-Met resulted in significant downregulation of TP53-induced Glycolysis and Apoptosis Regulator (TIGAR) and subsequent depletion of intracellular NADPH. Importantly, overexpression of TIGAR ameliorated the effects of c-Met kinase inhibition, confirming the importance of TIGAR downregulation in the growth inhibitory activity of c-Met TKI. The effects of c-Met inhibition on TIGAR and NADPH levels were observed with two different c-Met TKIs (AM7 and SU11274) and with multiple cell lines. As NADPH provides a crucial reducing power required for cell survival and proliferation, our findings reveal a novel mechanistic action of c-Met TKI, which may represent a key effect of c-Met kinase inhibition. Our data provide the first evidence linking c-Met, TIGAR and NADPH regulation in human cancer cells suggesting that inhibition of a tyrosine kinase/TIGAR/NADPH cascade may have therapeutic applicability in human cancers.
To compare astigmatic correction between femtosecond-assisted laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE).
A total of 111 patients were included in this ...prospective study. Fifty-seven eyes were treated with LASIK and 54 eyes were treated with SMILE for myopia with low to moderate (-0.25 to -4.0 D) astigmatism. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity and manifest refraction were measured preoperatively and at 1 and 3 months postoperatively. Visual and refractive outcomes were reported. Changes in refractive astigmatism were evaluated using vector analysis.
Preoperative characteristics were similar between both groups. The UDVA at 1 and 3 months was better in the LASIK group compared with the SMILE group (p<0.009). Postoperative cylinder was higher in the SMILE group (p<0.001). Fewer eyes attained the attempted cylindrical correction in the SMILE group (p<0.029). Vector analysis showed no significant difference in target-induced astigmatism (p=0.091) and angle of error (p>0.596) between the two groups. Surgically induced astigmatism was significantly lower in the SMILE group (p<0.023), while the difference vector (p<0.001) and absolute angle of error (p<0.016) were significantly higher in the SMILE group. No significant difference was found in these parameters between 1 and 3 months in both groups (p>0.122).
Our results showed that SMILE offered a less favourable astigmatic correction comparable to femtosecond-assisted LASIK in eyes with low to moderate myopic astigmatism. The alignment of treatment was more variable in SMILE, leading to a lower efficacy compared with LASIK by 3 months postoperatively.
Although much attention has been given to the global three-dimensional aspect of adolescent idiopathic scoliosis (AIS), the accurate three-dimensional morphology of the primary and compensatory ...curves, as well as the intervening junctional segments, in the scoliotic spine has not been described before.
A unique series of 77 AIS patients with high-resolution CT scans of the spine, acquired for surgical planning purposes, were included and compared to 22 healthy controls. Non-idiopathic curves were excluded. Endplate segmentation and local longitudinal axis in endplate plane enabled semi-automatic geometric analysis of the complete three-dimensional morphology of the spine, taking inter-vertebral rotation, intra-vertebral torsion and coronal and sagittal tilt into account. Intraclass correlation coefficients for interobserver reliability were 0.98-1.00. Coronal deviation, axial rotation and the exact length discrepancies in the reconstructed sagittal plane, as defined per vertebra and disc, were analyzed for each primary and compensatory curve as well as for the junctional segments in-between.
The anterior-posterior difference of spinal length, based on "true" anterior and posterior points on endplates, was +3.8% for thoracic and +9.4% for (thoraco)lumbar curves, while the junctional segments were almost straight. This differed significantly from control group thoracic kyphosis (-4.1%; P<0.001) and lumbar lordosis (+7.8%; P<0.001). For all primary as well as compensatory curves, we observed linear correlations between the coronal Cobb angle, axial rotation and the anterior-posterior length difference (r≥0.729 for thoracic curves; r≥0.485 for (thoraco)lumbar curves).
Excess anterior length of the spine in AIS has been described as a generalized growth disturbance, causing relative anterior spinal overgrowth. This study is the first to demonstrate that this anterior overgrowth is not a generalized phenomenon. It is confined to the primary as well as the compensatory curves, the junctional zones do not exhibit this growth discrepancy, however, they are straight.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite more than 30 years of searching, the compact object in Supernova (SN) 1987A has not yet been detected. We present new limits on the compact object in SN 1987A using millimeter, near-infrared, ...optical, ultraviolet, and X-ray observations from ALMA, VLT, HST, and Chandra. The limits are approximately 0.1 mJy ( erg s−1 cm−2 Hz−1) at 213 GHz, 1 L ( erg s−1 cm−2 Hz−1) in the optical if our line of sight is free of ejecta dust, and 1036 erg s−1 ( erg s−1 cm−2 Hz−1) in 2-10 keV X-rays. Our X-ray limits are an order of magnitude less constraining than previous limits because we use a more realistic ejecta absorption model based on three-dimensional neutrino-driven SN explosion models. The allowed bolometric luminosity of the compact object is 22 L if our line of sight is free of ejecta dust, or 138 L if dust-obscured. Depending on assumptions, these values limit the effective temperature of a neutron star (NS) to -8 MK and do not exclude models, which typically are in the range 3-4 MK. For the simplest accretion model, the accretion rate for an efficiency is limited to M yr−1, which excludes most predictions. For pulsar activity modeled by a rotating magnetic dipole in vacuum, the limit on the magnetic field strength (B) for a given spin period (P) is G s−2, which firmly excludes pulsars comparable to the Crab. By combining information about radiation reprocessing and geometry, we infer that the compact object is a dust-obscured thermally emitting NS, which may appear as a region of higher-temperature ejecta dust emission.
Highlights • The importance of patients' hand hygiene is increasingly recognized. • Directly observed patient hand hygiene for hospitalized patients is proposed. • Hand hygiene ambassadors are ...appointed to assist patient hand hygiene. • Ambassador-assisted patient hand hygiene achieves better compliance. • Empowerment of patients and ambassadors is equally important.
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