Analysis of a two-year independent screening effort for retinopathy of prematurity in rural Egypt

Background The third epidemic of retinopathy of prematurity (ROP) has majorly involved middle income countries in which tailored screening and local guidelines require development. The data regarding ROP prevalence and cutoff numbers for screening in Egypt are lacking. Methods Retrospective analysis of an independent screening effort spanning 2 years (February 2019 to February 2021) and involving 32 neonatal care units within Sharkia governorate, Egypt. Infants of gestational age (GA) ≤ 34 weeks and/or birth weight (BW) ≤ 2000 g were included, as well as those with unstable clinical course. Two eyecare centers located in Sharkia and Cairo governorates served as referral centers for any required interventions. Results Of the 276 screened infants, 133 (48.2%) had some form of ROP that was bilateral in 127 (95.5%) of them. Aggressive posterior ROP (AP-ROP) was detected in both eyes of 24 infants (8.7%). The median (IQR) GA of infants with ROP was 32 (30–34) weeks, and the median (IQR) BW was 1600 (1350–2000) g. Sixty-three infants (47.4%) required treatment. Of the total 84 eyes that primarily were treated, 73 (86.9%) received intravitreal ranibizumab, 8 (9.5%) underwent laser ablation therapy, and 3 eyes (3.6%) underwent surgery. Recurrence rate was 16.7% (14 eyes). Final outcome was favorable in 83 eyes (98.8%). Applying the American Academy criteria would have led to the missing of 36.8% of infants with ROP and 28.6% of those requiring treatment in our sample. Conclusion The incidence of both ROP and AP-ROP in the Egyptian rural setting appears to be in the high end of global reported rates. Prevention measures should urgently be planned and implemented.

Analysis of a Two-Year Independent Screening Effort for Retinopathy of Prematurity in Rural Egypt

Background: The third epidemic of retinopathy of prematurity (ROP) has majorly involved middle income countries in which tailored screening and local guidelines require development. The data regarding ROP prevalence and cutoff numbers for screening in Egypt are lacking.Methods: Retrospective analysis of an independent screening effort spanning 2 years and involving 32 neonatal care units within Sharkia governorate, Egypt. Infants of gestational age (GA) ≤ 34 weeks and/or birth weight (BW) ≤ 2000 g were included, as well as those with unstable clinical course. Two eyecare centers located in Sharkia and Cairo governorates served as referral centers for any required interventions.Results: Of the 276 screened infants, 133 (48.19%) had some form of ROP that was bilateral in 127 (95.49%) of them. Aggressive posterior ROP (AP-ROP) was detected in both eyes of 24 infants (8.7%). The median (IQR) GA of infants with ROP was 32 (30 - 34) weeks, and the median (IQR) BW was 1600 (1350 - 2000) g. Sixty-three infants (47.37%) required treatment. Of the total 84 eyes that were treated, 73 (86.9%) received intravitreal ranibizumab, 8 (9.52%) underwent laser ablation therapy, and 3 eyes (3.57%) underwent surgery. Primary outcome was favorable in 83 eyes (98.81%). Applying the American Academy criteria would have led to the missing of 36.84% of infants with ROP and 28.57% of those requiring treatment in our sample.Conclusion: The incidence of both ROP and AP-ROP in the Egyptian rural setting appears to be in the high end of global reported rates. Prevention measures should urgently be planned and implemented.

Scaling production of GFP1-10 detector protein in E. coli for secretion screening by split GFP assay

Background The split GFP assay is a well-known technology for activity-independent screening of target proteins. A superfolder GFP is split into two non-fluorescent parts, GFP11 which is fused to the target protein and GFP1-10. In the presence of both, GFP1-10 and the GFP11-tag are self-assembled and a functional chromophore is formed. However, it relies on the availability and quality of GFP1-10 detector protein to develop fluorescence by assembly with the GFP11-tag connected to the target protein. GFP1-10 detector protein is often produced in small scale shake flask cultivation and purified from inclusion bodies. Results The production of GFP1-10 in inclusion bodies and purification was comprehensively studied based on Escherichia coli as host. Cultivation in complex and defined medium as well as different feed strategies were tested in laboratory-scale bioreactor cultivation and a standardized process was developed providing high quantity of GFP1-10 detector protein with suitable quality. Split GFP assay was standardized to obtain robust and reliable assay results from cutinase secretion strains of Corynebacterium glutamicum with Bacillus subtilis Sec signal peptides NprE and Pel. Influencing factors from environmental conditions, such as pH and temperature were thoroughly investigated. Conclusions GFP1-10 detector protein production could be successfully scaled from shake flask to laboratory scale bioreactor. A single run yielded sufficient material for up to 385 96-well plate screening runs. The application study with cutinase secretory strains showed very high correlation between measured cutinase activity to split GFP fluorescence signal proofing applicability for larger screening studies.

Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.

VIF-Regression Screening Ultrahigh Dimensional Feature Space

Iterative Sure Independent Screening (ISIS) was proposed for the problem of variable selection with ultrahigh dimensional feature space. Unfortunately, the ISIS method transforms the dimensionality of features from ultrahigh to ultra-low and may result in un-reliable inference when the number of important variables particularly is greater than the screening threshold. The proposed method has transformed the ultrahigh dimensionality of features to high dimension space in order to remedy of losing some information by ISIS method. The proposed method is compared with ISIS method by using real data and simulation. The results show this method is more efficient and more reliable than ISIS method.

A High Autonomous Sea Front Detection Algorithm Based on SAR Data

This paper has proposed a high autonomous sea front detection algorithm based on SAR data. Through the innovative introduction of empirical mode decomposition method, a good image de-trend and de-stripe effect is achieved. By introducing the calculation of the maximum interclass variance, the automatic conversion of binary images is realized; through the use of polynomial fitting method, the independent screening of front information is realized, and the continuity of front detection results is improved. After comparison, it is found that the new algorithm proposed in this paper has greatly improved detection accuracy and autonomy compared with the old algorithm. Finally, a SAR data of the GF-3 satellite on the west side of Taiwan Island is used to test the new algorithm proposed in this paper. The results show that the detection results are highly consistent with the original image in morphology, and the changes in frontal intensity are also very detailed, verifying the accuracy and autonomy of the new method.

Decoding semi-automated title-abstract screening: findings from a convenience sample of reviews

Background We evaluated the benefits and risks of using the Abstrackr machine learning (ML) tool to semi-automate title-abstract screening and explored whether Abstrackr’s predictions varied by review or study-level characteristics. Methods For a convenience sample of 16 reviews for which adequate data were available to address our objectives (11 systematic reviews and 5 rapid reviews), we screened a 200-record training set in Abstrackr and downloaded the relevance (relevant or irrelevant) of the remaining records, as predicted by the tool. We retrospectively simulated the liberal-accelerated screening approach. We estimated the time savings and proportion missed compared with dual independent screening. For reviews with pairwise meta-analyses, we evaluated changes to the pooled effects after removing the missed studies. We explored whether the tool’s predictions varied by review and study-level characteristics. Results Using the ML-assisted liberal-accelerated approach, we wrongly excluded 0 to 3 (0 to 14%) records that were included in the final reports, but saved a median (IQR) 26 (9, 42) h of screening time. One missed study was included in eight pairwise meta-analyses in one systematic review. The pooled effect for just one of those meta-analyses changed considerably (from MD (95% CI) − 1.53 (− 2.92, − 0.15) to − 1.17 (− 2.70, 0.36)). Of 802 records in the final reports, 87% were correctly predicted as relevant. The correctness of the predictions did not differ by review (systematic or rapid, P = 0.37) or intervention type (simple or complex, P = 0.47). The predictions were more often correct in reviews with multiple (89%) vs. single (83%) research questions (P = 0.01), or that included only trials (95%) vs. multiple designs (86%) (P = 0.003). At the study level, trials (91%), mixed methods (100%), and qualitative (93%) studies were more often correctly predicted as relevant compared with observational studies (79%) or reviews (83%) (P = 0.0006). Studies at high or unclear (88%) vs. low risk of bias (80%) (P = 0.039), and those published more recently (mean (SD) 2008 (7) vs. 2006 (10), P = 0.02) were more often correctly predicted as relevant. Conclusion Our screening approach saved time and may be suitable in conditions where the limited risk of missing relevant records is acceptable. Several of our findings are paradoxical and require further study to fully understand the tasks to which ML-assisted screening is best suited. The findings should be interpreted in light of the fact that the protocol was prepared for the funder, but not published a priori. Because we used a convenience sample, the findings may be prone to selection bias. The results may not be generalizable to other samples of reviews, ML tools, or screening approaches. The small number of missed studies across reviews with pairwise meta-analyses hindered strong conclusions about the effect of missed studies on the results and conclusions of systematic reviews.

Does Mind-Wandering Relate to Mood and Stress in Young Adults? A Narrative Review

Mind-wandering (MW) is ubiquitous and has been extensively studied in young adults. Studies have shown that MW, daydreaming, and sluggish cognitive tempo symptoms (SCT; e.g., staring, mental fogginess, confusion, hypoactivity, sluggishness, lethargy, and drowsiness) are interrelated constructs and all relate to mood and stress-related symptoms. The aims of the current review are to a) document the associations between MW (and related constructs: daydreaming, and SCT) and mood/stress-related symptoms (e.g., anxiety and depression symptoms) in young adults and b) identify potential mechanisms underlying these relationships. We conducted a narrative review of the literature on the subject. We searched MEDLINE (Ovid) and PsycINFO® (Ovid) databases and performed duplicate and independent screening. A total of 559 unique records were identified, and 22 records (published between 1978 and 2017) were included. We confirmed existing evidence of the associations between MW, daydreaming, SCT and mood/stress-related symptoms in young adults (aged 18 - 30 years). Although these associations are reported, our understanding of its directionality and underlying mechanisms remains incomplete. These findings highlight the need for further research combining experimental and correlational designs and including possible mechanisms of these associations in this population.

Decoding semi-automated title-abstract screening: findings from a convenience sample of reviews

Background. We evaluated the benefits and risks of using the Abstrackr machine learning (ML) tool to semi-automate title-abstract screening, and explored whether Abstrackr’s predictions varied by review or study-level characteristics.Methods. For a convenience sample of 16 reviews for which adequate data were available to address our objectives (11 systematic reviews and 5 rapid reviews) we screened a 200-record training set in Abstrackr and downloaded the relevance (relevant or irrelevant) of the remaining records, as predicted by the tool. We retrospectively simulated the liberal-accelerated screening approach. We estimated the time savings and proportion missed compared with dual independent screening. For reviews with pairwise meta-analyses, we evaluated changes to the pooled effects after removing the missed studies. We explored whether the tool’s predictions varied by review and study-level.Results. Using the ML-assisted liberal-accelerated approach, we wrongly excluded 0 to 3 (0 to 14%) records that were included in the final reports, but saved a median (IQR) 26 (9, 42) hours of screening time. One missed study was included in eight pairwise meta-analyses in one systematic review. The pooled effect for just one of those meta-analyses changed considerably (from MD (95% CI) -1.53 (-2.92, -0.15) to -1.17 (-2.70, 0.36)). Of 802 records in the final reports, 87% were correctly predicted as relevant. The correctness of the predictions did not differ by review (systematic or rapid, P=0.37) or intervention type (simple or complex, P=0.47). The predictions were more often correct in reviews with multiple (89%) vs. single (83%) research questions (P=0.01), or that included only trials (95%) vs. multiple designs (86%) (P=0.003). At the study level, trials (91%), mixed methods (100%), and qualitative (93%) studies were more often correctly predicted as relevant compared with observational studies (79%) or reviews (83%) (P=0.0006). Studies at high or unclear (88%) vs. low risk of bias (80%) (P=0.039), and those published more recently (mean (SD) 2008 (7) vs. 2006 (10), P=0.02) were more often correctly predicted as relevant.Conclusion. Our screening approach saved time and may be suitable in conditions where the limited risk of missing relevant records is acceptable. As several of our findings are paradoxical, and require further study to fully understand the tasks to which ML-assisted screening is best suited. The findings should be interpreted in light of the fact that the protocol was prepared for the funder, but not published a priori. Because we used a convenience sample the findings may be prone to selection bias. The results may not be generalizable to other samples of reviews, ML tools, or screening approaches. The small number of missed studies across reviews with pairwise meta-analyses hindered strong conclusions about the effect of missed studies on the results and conclusions of systematic reviews.