Search

Emergence of the colistin resistance gene, mcr-1, has attracted worldwide attention. Despite the prevalence of mcr-1-positive Escherichia coli (MCRPEC) strains in human carriage showing a significant decrease between 2016 and 2019, genetic differences in MCRPEC strains remain largely unknown. We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019. We identified three major differences in MCRPEC strains between these two time points. First, the insertion sequence ISApl1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019. Second, the antibiotic resistance genes (ARGs), aac(3)-IVa and blaCTX-M-1, emerged and coexisted with mcr-1 in 2019. Third, MCRPEC strains in 2019 contained more virulence genes, resulting in an increased proportion of extraintestinal pathogenic E. coli (ExPEC) strains (36.1%) in MCRPEC strains in 2019 compared to that in 2016 (10.5%), implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria. Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019, MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes, which may pose a potential public health threat.

Ocular surface disease can be difficult to manage, causing patients discomfort and vision loss. Therapeutic contact lenses are an important treatment option that is often neglected because it is conventional wisdom that eyes that are dry or irritated are not good candidates for contact lens. In this focused review, we consider the substantial literature on the use of bandage soft contact lenses (BSCL), scleral lenses, and customized prosthetic devices in the management of ocular graft-vs-host disease. Reports on BSCLs for recurrent corneal erosion are reviewed, as is literature on scleral lenses and prosthetic replacement of the ocular surface ecosystem treatment for Stevens-Johnson syndrome. Clinical pearls for fitting BSCLs are presented, and the issue of antibiotic prophylaxis is considered.

Bombyx mori is an important economic insect, its economic value mainly reflected in the silk yield. The major functional genes affecting the silk yield of B. mori have not been determined yet. Bombyx mori vacuolar protein sorting-associated protein 13d (BmVps13d) has been identified, but its function is not reported. In this study, BmVps13d protein shared 30.84% and 34.35% identity with that of in Drosophila melanogaster and Homo. sapiens, respectively. The expressions of BmVps13d were significantly higher in the midgut and silk gland of JS (high silk yield) than in that of L10 (low silk yield). An insertion of 9 bp nucleotides and two deficiencies of adenine ribonucleotides in the putative promoter region of BmVps13d gene in L10 resulted in the decline of promoter activity was confirmed using dual luciferase assay. Finally, the functions of BmVps13d in B. mori were studied using the CRISPR/Cas9 system, and the mutation of BmVps13d resulted in a 24.7% decline in weight of larvae, as well as a 27.1% (female) decline and a 11.8% (male) decline in the silk yield. This study provides a foundation for studying the molecular mechanism of silk yield and breeding the silkworm with high silk yield.

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types., Graphical abstract, D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.

There is increasing evidence that pelvic mobility is a critical factor to consider in implant alignment during total hip arthroplasty (THA). Here, we test the feasibility of using an inertial sensor fitted across the sacrum to measure change in pelvic tilt, and hence screen for patients with high pelvic mobility. Patients (n = 32, mean age: 57.4 years) due to receive THA surgery participated in the study. Measures of pelvic tilt were captured simultaneously using the device and radiograph in three functional positions: Standing, flexed-seated, and step-up. We found a strong correlation between the device and radiograph measures for the change in pelvic tilt measure from standing to flexed-seated position (R2 = 0.911), 75% of absolute errors were under 5 degrees. We demonstrated that the device can be used as a screening tool to rapidly identify patients who would benefit from more detailed surgical planning of implant positioning to reduce future risks of impingement and dislocation.

Openness to experience and divergent thinking are considered to be critical in real-life creative achievement. However, there is still a lack of neural evidence to explain how creative achievement is related to openness to experience and divergent thinking. Here, a structural equation model and resting-state functional connectivity were used to investigate their relationships in college students. The structural equation model results repeatedly showed that openness to experience and divergent thinking are positively associated with creative achievement, and the resting-state functional connectivity results showed that openness to experience and divergent thinking were both correlated with the attention network and default mode network. However, openness to experience was also correlated with the primary sensorimotor network and frontoparietal control network. Mediation models further corroborated this result. Collectively, these findings support previous works and further indicate that different neural bases may underlie the associations of creative achievement with openness to experience and divergent thinking.

Following the discovery and emergence of the plasmid-mediated colistin resistance gene, mcr-1, the Chinese government formally banned colistin as an animal growth promoter on April 30, 2017. Herein, we report patterns in colistin resistance and mcr-1 abundance in Escherichia coli from animals and humans between 2015 and 2019, to evaluate the effects of the colistin withdrawal.We did an epidemiology comparative study to investigate: annual production and sales of colistin in agriculture across mainland China according to data from the China Veterinary Drug Association from 2015 to 2018; the prevalence of colistin-resistant E coli (CREC) in pigs and chickens in 23 Chinese provinces and municipalities as reported in the China Surveillance on Antimicrobial Resistance of Animal Origin database from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2017, to Dec 31, 2018; the presence of residual colistin and mcr-1 in faeces from 118 animal farms (60 pig, 29 chicken, and 29 cattle) across four provinces over July 1, 2017, to August 31, 2017, and July 1, 2018 to August 31, 2018; the prevalence of mcr-1-positive E coli (MCRPEC) carriage in healthy individuals attending routine hospital examinations across 24 provinces and municipalities from June 1 to July 30, 2019, comparing with equivalent 2016 data (June 1 to September 30) from our previous study in the same hospitals; and the patterns in CREC prevalence among hospital E coli infections across 26 provinces and municipalities from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2018, to Dec 31, 2019, reported on the China Antimicrobial Surveillance Network.After the ban on colistin as a growth promoter, marked reductions were observed in the production (27 170 tonnes in 2015 vs 2497 tonnes in 2018) and sale (US$71·5 million in 2015 vs US$8·0 million in 2018) of colistin sulfate premix. Across 118 farms in four provinces, mean colistin residue concentration was 191·1 μg/kg (SD 934·1) in 2017 versus 7·5 μg/kg (50·0) in 2018 (p0·0001), and the median relative abundance of mcr-1 per 16S RNA was 0·0009 [IQR 0·0001-0·0059] in 2017 versus 0·0002 [0·0000-0·0020] in 2018 (p=0·0001). Across 23 provinces and municipalities, CREC was identified in pig faeces in 1153 (34·0%) of 3396 samples in 2015-16 versus 142 (5·1%) of 2781 in 2017-18 (p0·0001); and in chickens in 474 (18·1%) of 2614 samples in 2015-16 versus 143 (5·0%) of 2887 in 2017-18 (p0·0001). In hospitals across 24 provincial capital cities and municipalities, human carriage of MCRPEC was identified in 644 (14·3%) of 4498 samples in 2016 versus 357 (6·3%) of 5657 in 2019 (p0·0001). Clinical CREC infections in 26 provinces and municipalities comprised 1059 (1·7%) of 62 737 E coli infections in 2015-16 versus 794 (1·3%) of 59 385 in 2018-19 (p0·0001).The colistin withdrawal policy and the decreasing use of colistin in agriculture have had a significant effect on reducing colistin resistance in both animals and humans in China. However, continuous colistin monitoring is essential, in particular to act as an early warning system for colistin stewardship in Chinese hospitals.National Key Research and Development Program of China, National Natural Science Foundation of China, and UK Medical Research Council.

To assess how ocular ultrasound findings correlate with clinical parameters of patients with infectious keratitis and concern for endophthalmitis and to evaluate the usefulness of ultrasound in managing these patients.Retrospective study.Seventy-three eyes of 73 patients with microbial keratitis who underwent ultrasound to evaluate for endophthalmitis were included.Ultrasound images were graded in a masked fashion independently by 2 retina specialists. The degree of vitreous opacities, defined as the largest area within the vitreous cavity occupied by opacities on any single image, were categorized as less than 10%, 10% to less than 50%, 50% to 90%, and more than 90%. The diagnosis of endophthalmitis was defined as severe intraocular inflammation that necessitated obtaining an intraocular culture sample and injection of intravitreal antimicrobials. The demographic and clinical characteristics of this patient cohort were compared.Vitreous opacities measured quantitatively on ocular ultrasound.The incidence of endophthalmitis in our patients with microbial keratitis who underwent ultrasound was 20.5%. Corneal and intraocular cultures showed positive results in 66.7% and 26.7% of endophthalmitis patients, respectively. A 4-fold increase in the likelihood of treatment for endophthalmitis was observed with increasing vitreous opacity severity (odds ratio, 3.97; confidence interval, 1.9-8.5; P0.0001). Endophthalmitis was associated with 50% or more vitreous opacities (P0.001), older age (P0.001), pseudophakia (P = 0.001), and hypopyon height (P0.001). Eye pain, eyelid edema, poor presenting visual acuity, larger corneal ulcer diameter, and causative organisms were not associated with endophthalmitis.Patients with more severe vitreous opacities on ultrasound were more likely to be treated for endophthalmitis. Patients with microbial keratitis, who were older and pseudophakic, were prone to have more severe vitreous opacities.

Background To determine which resident and program characteristics correlate with ophthalmic knowledge, as assessed by resident Ophthalmic Knowledge Assessment Program (OKAP) performance. Methods An online survey was sent in June 2017 to all US ophthalmology residents who took the OKAP in April 2017. Results The survey response rate was 13.8% (192/1387 residents). The mean respondent age was 30.4 years, and 57.3% were male. The mean [SD] self-reported 2017 OKAP percentile was 61.9 [26.7]. OKAP performance was found to have a significant positive correlation with greater number of hours spent/week studying for the OKAPs (p = 0.007), with use of online question banks (p

CDH1 (also known as E-cadherin), an epithelial-specific cell–cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a hallmark of epithelial-to-mesenchymal transition (EMT) and correlates with poor prognosis in multiple carcinomas. Conversely, upregulation of E-cadherin is prognostic for improved survival in sarcomas. Yet, despite the prognostic benefit of E-cadherin expression in sarcoma, the mechanistic significance of E-cadherin in sarcomas remains poorly understood. Here, by combining mathematical models with wet-bench experiments, we identify the core regulatory networks mediated by E-cadherin in sarcomas, and decipher their functional consequences. Unlike carcinomas, E-cadherin overexpression in sarcomas does not induce a mesenchymal-to-epithelial transition (MET). However, E-cadherin acts to reduce both anchorage-independent growth and spheroid formation of sarcoma cells. Ectopic E-cadherin expression acts to downregulate phosphorylated CREB1 (p-CREB) and the transcription factor, TBX2, to inhibit anchorage-independent growth. RNAi-mediated knockdown of TBX2 phenocopies the effect of E-cadherin on CREB levels and restores sensitivity to anchorage-independent growth in sarcoma cells. Beyond its signaling role, E-cadherin expression in sarcoma cells can also strengthen cell–cell adhesion and restricts spheroid growth through mechanical action. Together, our results demonstrate that E-cadherin inhibits sarcoma aggressiveness by preventing anchorage-independent growth. Implications: We highlight how E-cadherin can restrict aggressive behavior in sarcomas through both biochemical signaling and biomechanical effects.

PURPOSE OF REVIEW Crowdsourcing involves the use of the collective intelligence of online communities to produce solutions and outcomes for defined objectives. The use of crowdsourcing is growing in many scientific areas. Crowdsourcing in ophthalmology has been used in basic science and clinical research; however, it also shows promise as a method with wide-ranging applications. This review presents current findings on the use of crowdsourcing in ophthalmology and potential applications in the future. RECENT FINDINGS Crowdsourcing has been used to distinguish normal retinal images from images with diabetic retinopathy; the collective intelligence of the crowd was able to correctly classify 81% of 230 images (19 unique) for US$1.10/eye in 20 min. Crowdsourcing has also been used to distinguish normal optic discs from abnormal ones with reasonable sensitivity (83-88%), but low specificity (35-43%). Another study used crowdsourcing for quick and reliable manual segmentation of optical coherence tomography images. Outside of ophthalmology, crowdsourcing has been used for text and image interpretation, language translation, and data analysis. SUMMARY Crowdsourcing has the potential for rapid and economical data processing. Among other applications, it could be used in research settings to provide the 'ground-truth' data, and in the clinical settings to relieve the burden of image processing on experts.

People attend to the same event or object by using a global or local processing style across different environments. Different physical environmental conditions, such as orderliness and disorderliness, activate different psychological states and produce different kinds of outcomes. However, previous work has rarely examined whether individuals exposed to different orderly or disorderly environments attend to the “global” or the “local” differently. Thus, in the current study, we conducted three behavioral experiments to directly examine the impact of disorder versus order cues on people's types of perceptual and conceptual processing (global vs. local). We asked participants to perform a typical Kimchi–Palmer figures task or a categorization task: with pre‐primed disorderly or orderly physical environmental pictures (Experiment 1), with basic visual pictures (Experiment 2), and imagining a real environment (Experiment 3). The results revealed that in any of the above operations, orderly experience led to global perceptual processing, whereas disorderly experience led to local perceptual processing. This difference in processing style was not influenced by the participants’ daily habits or their preference for the need for structure. However, this difference in perceptual processing style did not spill over to the conceptual processing style. These findings provide direct evidence of the effects of disorderliness versus orderliness on global versus local perceptual and conceptual processing and imply that environmental orderliness or disorderliness may functionally affect cognitive processing (i.e., how we see and think about events and objects). Thus, the findings creatively bridge several lines of research and shed light on a basic cognitive mechanism responsible for perceptions of order/disorder.

As the number of people with diabetic retinopathy (DR) in the USA is expected to increase threefold by 2050, the need to reduce health care costs associated with screening for this treatable disease is ever present. Crowdsourcing and automated retinal image analysis (ARIA) are two areas where new technology has been applied to reduce costs in screening for DR. This paper reviews the current literature surrounding these new technologies. Crowdsourcing has high sensitivity for normal vs abnormal images; however, when multiple categories for severity of DR are added, specificity is reduced. ARIAs have higher sensitivity and specificity, and some commercial ARIA programs are already in use. Deep learning enhanced ARIAs appear to offer even more improvement in ARIA grading accuracy. The utilization of crowdsourcing and ARIAs may be a key to reducing the time and cost burden of processing images from DR screening.

Background: Diabetic retinopathy (DR) is a leading cause of vision loss in working age individuals worldwide. While screening is effective and cost effective, it remains underutilized, and novel methods are needed to increase detection of DR. This clinical validation study compared diagnostic gradings of retinal fundus photographs provided by volunteers on the Amazon Mechanical Turk (AMT) crowdsourcing marketplace with expert-provided gold-standard grading and explored whether determination of the consensus of crowdsourced classifications could be improved beyond a simple majority vote (MV) using regression methods. Objective: The aim of our study was to determine whether regression methods could be used to improve the consensus grading of data collected by crowdsourcing. Methods: A total of 1200 retinal images of individuals with diabetes mellitus from the Messidor public dataset were posted to AMT. Eligible crowdsourcing workers had at least 500 previously approved tasks with an approval rating of 99% across their prior submitted work. A total of 10 workers were recruited to classify each image as normal or abnormal. If half or more workers judged the image to be abnormal, the MV consensus grade was recorded as abnormal. Rasch analysis was then used to calculate worker ability scores in a random 50% training set, which were then used as weights in a regression model in the remaining 50% test set to determine if a more accurate consensus could be devised. Outcomes of interest were the percent correctly classified images, sensitivity, specificity, and area under the receiver operating characteristic (AUROC) for the consensus grade as compared with the expert grading provided with the dataset. Results: Using MV grading, the consensus was correct in 75.5% of images (906/1200), with 75.5% sensitivity, 75.5% specificity, and an AUROC of 0.75 (95% CI 0.73-0.78). A logistic regression model using Rasch-weighted individual scores generated an AUROC of 0.91 (95% CI 0.88-0.93) compared with 0.89 (95% CI 0.86-92) for a model using unweighted scores (chi-square P value

PURPOSE To assess the accuracy of crowdsourcing for grading optic nerve images for glaucoma using Amazon Mechanical Turk before and after training modules. MATERIALS AND METHODS Images (n=60) from 2 large population studies were graded for glaucoma status and vertical cup-to-disc ratio (VCDR). In the baseline trial, users on Amazon Mechanical Turk (Turkers) graded fundus photos for glaucoma and VCDR after reviewing annotated example images. In 2 additional trials, Turkers viewed a 26-slide PowerPoint training or a 10-minute video training and passed a quiz before being permitted to grade the same 60 images. Each image was graded by 10 unique Turkers in all trials. The mode of Turker grades for each image was compared with an adjudicated expert grade to determine accuracy as well as the sensitivity and specificity of Turker grading. RESULTS In the baseline study, 50% of the images were graded correctly for glaucoma status and the area under the receiver operating characteristic (AUROC) was 0.75 [95% confidence interval (CI), 0.64-0.87]. Post-PowerPoint training, 66.7% of the images were graded correctly with AUROC of 0.86 (95% CI, 0.78-0.95). Finally, Turker grading accuracy was 63.3% with AUROC of 0.89 (95% CI, 0.83-0.96) after video training. Overall, Turker VCDR grades for each image correlated with expert VCDR grades (Bland-Altman plot mean difference=-0.02). CONCLUSIONS Turkers graded 60 fundus images quickly and at low cost, with grading accuracy, sensitivity, and specificity, all improving with brief training. With effective education, crowdsourcing may be an efficient tool to aid in the identification of glaucomatous changes in retinal images.