Role of corneal biomechanical properties in predicting of speed of myopic progression in children wearing orthokeratology lenses or single-vision spectacles

Objective To determine the characteristics of children who were likely to progress rapidly and gain the greatest benefit from orthokeratology (ortho-k) treatment. Methods and analysis The files of 113 children who participated in two myopia control studies and wore either ortho-k lenses (n=62) or single-vision spectacles (SVS) (n=51) were reviewed. Baseline cycloplegic subjective refraction, central corneal thickness, axial length, keratometry, intraocular pressure, corneal biomechanical properties and 24-month axial length data were retrieved and analysed. Results Multivariate analysis showed that there was significant negative correlation between axial elongation and baseline age and corneal hysteresis (p<0.05) in the SVS group. In the ortho-k group, only baseline age was significantly and negatively associated with axial elongation (p<0.01). Conclusion Corneal biomechanical properties and baseline age can predict the rate of axial elongation in myopic children. It may be beneficial for younger myopic children with low corneal hysteresis to commence ortho-k treatment as early as possible

Repeatability of corneal biomechanics waveform signal parameters derived from Ocular Response Analyzer in children

Purpose To investigate the repeatability of waveform signal parameters, measured with the Ocular Response Analyzer (ORA), in children. Methods Two sets of ORA measurements, with a 10-min break between them, were performed on children, aged six to 0.90 (regarded as moderate to excellent agreement). Results A total of 30 participants [15 SVS, 15 ortho-k (3.6 ± 2.4 months)] completed the study. Since no significant between-group differences were detected in demographic data (p > 0.28) and all waveform signal parameters (p > 0.05), data from the two groups of participants were pooled for the analysis of repeatability. Six parameters, h2, h21, p1area, p1area1, p2area, and p2area1, achieved ICCs (95 % CI) of 0.82−0.85 (0.61−0.93). The mean (SD) of these six parameters were 372 (91), 248 (61), 4077 (854), 1762 (399), 2359 (670), and 1020 (300), respectively. Bland-Altman plots and 95 % limits of agreement (95 % LoA) showed considerable agreement for all six parameters, the mean difference (95 % LoA) were -3 (-101 to 94), -2 (-67.56–62.70), 111 (-723 to 946), 102 (-334 to 539), 25 (-718 to 768), and -3 (-350 to 343), respectively. Conclusions Six waveform signal parameters (h2, h21, p1area, p1area1, p2area, and p2area1), which represent or are related to the areas under the waveform at the peaks in the signal, had moderate to excellent agreement in children. Results of the current study provides fundamental information for further studies on the potential clinical application of these waveform signal parameters in children

C-Terminal Binding Protein 2 Is a Novel Tumor Suppressor Targeting the Myc-Irf4 axis in Multiple Myeloma

Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered undruggable, as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy

Key determinants of willingness to support policy measures on recycling: a case study in Hong Kong

2015-2016 > Academic research: refereed > Publication in refereed journa

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Prebiotics and Dietary Fibers from Food Processing By-Products

The abundance of agricultural wastes or by-products from industrial and domesti- Q1 cated food processing is the main cause of environment problems. These by-products are generally managed by disposal or even sold at a cheaper price. Disposal of these underutilized by-products are commonly done in inappropriate ways, i.e. discharge effluent into rivers or by burning in the open, which may cause air and water pollutions. Presently, scientific investigation on the benefits or functional properties of waste and by-products from industrial food processing, which produces a large amount of by-products, is necessary in the search for possible ways for their utilization (Vanesa et al., 2011). Three main groups of by-product from food processing, classified according to their main chemical compositions, are carbohydrate and dietary fibers, protein and lipids. The most common by-products are generated by the food industry, in particular the beverage, starch and flour industries. These items are classified under carbohydrate and dietary fiber groups. They are further divided into four sub-groups: monosaccharides, disaccharides, oligosaccharides and polysaccharides. Dietary fibers are a class of non-starch polysaccharides (i.e. cellulose, dextrins, chitins, pectins, β-glucans and waxes) and lignin, which are able to modulate the transit time through the gut. Thus, it provides similar beneficial effects to those of inulin-type fructans. These compounds are commonly found in many foods such as cereal, nuts etc. They are also partially susceptible to bacterial fermentation and may induce changes in bacterial populations, particularly in the numerous bifidobacteria and lactobacilli. These soluble dietary fibers have been shown to exert additional beneficial effects, for instance by improving gut barrier function in vitro and in vivo, which could be partially a consequence of their effect on the microflora composition (Laparra and Sanz, 2010)