Nevin Manimala

Sci Transl Med. 2024 May 22;16(748):eadj3385. doi: 10.1126/scitranslmed.adj3385. Epub 2024 May 22.

ABSTRACT

Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5′-cytosine-phosphate-guanine-3′ loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10^-14. In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.

PMID:38776390 | DOI:10.1126/scitranslmed.adj3385

Sci Robot. 2024 May 22;9(90):eadj8812. doi: 10.1126/scirobotics.adj8812. Epub 2024 May 22.

ABSTRACT

To enhance wearable robots, understanding user intent and environmental perception with novel vision approaches is needed.

PMID:38776377 | DOI:10.1126/scirobotics.adj8812

Proc Natl Acad Sci U S A. 2024 May 28;121(22):e2319249121. doi: 10.1073/pnas.2319249121. Epub 2024 May 22.

ABSTRACT

The consistency of energy landscape theory predictions with available experimental data, as well as direct evidence from molecular simulations, have shown that protein folding mechanisms are largely determined by the contacts present in the native structure. As expected, native contacts are generally energetically favorable. However, there are usually at least as many energetically favorable nonnative pairs owing to the greater number of possible nonnative interactions. This apparent frustration must therefore be reduced by the greater cooperativity of native interactions. In this work, we analyze the statistics of contacts in the unbiased all-atom folding trajectories obtained by Shaw and coworkers, focusing on the unfolded state. By computing mutual cooperativities between contacts formed in the unfolded state, we show that native contacts form the most cooperative pairs, while cooperativities among nonnative or between native and nonnative contacts are typically much less favorable or even anticooperative. Furthermore, we show that the largest network of cooperative interactions observed in the unfolded state consists mainly of native contacts, suggesting that this set of mutually reinforcing interactions has evolved to stabilize the native state.

PMID:38776371 | DOI:10.1073/pnas.2319249121

PLoS One. 2024 May 22;19(5):e0302870. doi: 10.1371/journal.pone.0302870. eCollection 2024.

ABSTRACT

The systematic identification of insertion/deletion (InDel) length polymorphisms from the entire lentil genome can be used to map the quantitative trait loci (QTL) and also for the marker-assisted selection (MAS) for various linked traits. The InDels were identified by comparing the whole-genome resequencing (WGRS) data of two extreme bulks (early- and late-flowering bulk) and a parental genotype (Globe Mutant) of lentil. The bulks were made by pooling 20 extreme recombinant inbred lines (RILs) each, derived by crossing Globe Mutant (late flowering parent) with L4775 (early flowering parent). Finally, 734,716 novel InDels were identified, which is nearly one InDel per 5,096 bp of lentil genome. Furthermore, 74.94% of InDels were within the intergenic region and 99.45% displayed modifier effects. Of these, 15,732 had insertions or deletions of 20 bp or more, making them amenable to the development of PCR-based markers. An InDel marker I-SP-356.6 (chr. 3; position 356,687,623; positioned 174.5 Kb from the LcFRI gene) was identified as having a phenotypic variance explained (PVE) value of 47.7% for earliness when validated in a RIL population. Thus, I-SP-356.6 marker can be deployed in MAS to facilitate the transfer of the earliness trait to other elite late-maturing cultivars. Two InDel markers viz., I-SP-356.6 and I-SP-383.9 (chr. 3; linked to LcELF3a gene) when tested in 9 lentil genotypes differing for maturity duration, clearly distinguished three early (L4775, ILL7663, Precoz) and four late genotypes (Globe Mutant, MFX, L4602, L830). However, these InDels could not be validated in two genotypes (L4717, L4727), suggesting either absence of polymorphism and/or presence of other loci causing earliness. The identified InDel markers can act as valuable tools for MAS for the development of early maturing lentil varieties.

PMID:38776345 | DOI:10.1371/journal.pone.0302870

PLoS One. 2024 May 22;19(5):e0304239. doi: 10.1371/journal.pone.0304239. eCollection 2024.

ABSTRACT

BACKGROUND: At the end of 2022, globally, only 46% of children (aged 0-14 years) on ART had suppressed viral loads. Viral load suppression is crucial to reduce HIV-related deaths. To suppress the viral load at the expected level, children must be retained in ART treatment. Nevertheless, lost to follow-up from ART treatment continues to be a global challenge, particularly, in developing countries. Previously, primary studies were conducted in Ethiopia to assess the incidence of lost to follow-up among HIV-positive children on ART treatment. However, variations have been seen among the studies. Therefore, this systematic review and meta-analysis aimed to estimate the pooled incidence of lost to follow-up among HIV-positive children on ART and identify its associated factors in Ethiopia.

METHODS: We searched PubMed, HINARI, Science Direct, Google Scholar, and African Journals Online to obtain articles published up to November 20, 2023. Critical appraisal was done using the Joanna Briggs Institute checklist. Heterogeneity was identified using I-square statistics. Funnel plot and Egger’s tests were used to identify publication bias. Data was presented using forest plots and tables. Random and fixed-effect models were used to compute the pooled estimate.

RESULTS: Twenty-four studies were included in the final analysis. The pooled incidence of lost to follow-up among HIV-positive children on ART was 2.79 (95% CI: 1.99, 3.91) per 100-child-year observations. Advanced HIV disease (HR: 2.20, 95% CI: 1.71, 2.73), having opportunistic infection (HR: 2.59, 95% CI: 1.39; 4.78), fair or poor ART treatment adherence (HR: 2.92, 95% CI: 1.31; 6.54) and children aged between 1-5 years (HR: 2.1,95% CI: 1.44; 2.95) were factors associated with lost to follow up among HIV positive children on ART.

CONCLUSIONS: The overall pooled incidence of lost to follow-up among HIV-positive children on ART is low in Ethiopia. Therefore, counseling on ART drug adherence should be strengthened. Moreover, emphasis has to be given to children with advanced HIV stage and opportunistic infection to reduce the rate of lost to follow up among HIV-positive children on ART.

TRIAL REGISTRATION: Registered in PROSPERO with ID: CRD42024501071.

PMID:38776343 | DOI:10.1371/journal.pone.0304239

PLoS One. 2024 May 22;19(5):e0294371. doi: 10.1371/journal.pone.0294371. eCollection 2024.

ABSTRACT

PURPOSE: To determine the prevalence and causes of blindness and visual impairment among adults in Kogi, Nigeria.

METHODS: A Rapid assessment of avoidable blindness (RAAB) protocol was used with additional tools measuring disability and household wealth to measure the prevalence of blindness and visual impairment (VI) and associations with sex, disability, wealth, cataract surgical coverage and its effectiveness.

RESULTS: Age- and sex-adjusted all-cause prevalence of bilateral blindness was 3.6% (95%CI 3.0-4.2%), prevalence of blindness among people living with additional, non-visual disabilities was 38.3% (95% CI 29.0-48.6%) compared to 1.6% (95%CI 1.2-2.1%; [Formula: see text] = 771.9, p<0.001) among people without additional disabilities. Cataract was the principal cause of bilateral blindness (55.3%). Cataract surgical coverage (CSC) at visual acuity (VA) 3/60 was 48.0%, higher among men than women (53.7% vs 40.3%); 12.0% among people with non-visual disabilities; 66.9% among people without non-visual disabilities, being higher among people in the wealthiest two quintiles (41.1%) compared to the lowest three (24.3%). Effective Cataract Surgical Coverage at Visual Acuity 6/60 was 31.0%, higher among males (34.9%) than females (25.5%), low among people with additional, non-visual disabilities (1.9%) compared to people with no additional disabilities (46.2%). Effective CDC was higher among people in the wealthiest two quintiles (411%) compared to the poorest three (24.3%). Good surgical outcome (VA>6/18) was seen in 61 eyes (52.6%) increasing to 71 (61.2%) eyes with best correction. Cost was identified as the main barrier to surgery.

CONCLUSION: Findings suggest there exists inequalities in eye care with women, poorer people and people with disabilities having a lower Cataract Surgical Coverage, thereby, underscoring the importance of eye care programs to address these inequalities.

PMID:38776330 | DOI:10.1371/journal.pone.0294371

PLoS One. 2024 May 22;19(5):e0304156. doi: 10.1371/journal.pone.0304156. eCollection 2024.

ABSTRACT

Saliva substitutes with enhanced dentin remineralization properties were expected to help manage caries progression in patients with xerostomia. This in vitro study examined the rheological properties and remineralization action of experimental saliva substitutes containing propolis extract and aloe vera extract on demineralized dentin. Four experimental saliva substitutes were formulated with varying concentrations of propolis extract (P) and aloe vera extract (A) were prepared. A commercial saliva substitute (Biotene Oral Rinse) was used as a commercial comparison. The rheological properties and viscosity of these materials were measured using a strain-controlled rheometer (n = 3). The remineralizing actions of saliva substitutes on demineralized dentin after 2 weeks were determined using ATR-FTIR and SEM-EDX (n = 8). The results were expressed as a percentage increase in the mineral-to-matrix ratio. Biotene demonstrated a significantly higher viscosity (13.5 mPa·s) than experimental saliva substitutes (p<0.05). The addition of extracts increased the viscosity of the saliva substitutes from 4.7 mPa·s to 5.2 mPa·s. All formulations showed minimal shear thinning behavior, which was the viscoelastic properties of natural saliva. The formulation containing 5 wt% of propolis exhibited the highest increase in the median mineral-to-matrix ratio (25.48%). The SEM-EDX analysis revealed substantial mineral precipitation in demineralized dentin, especially in formulations with 5 wt% or 2.5 wt% of propolis. The effect of the aloe vera extract was minimal. The addition of propolis and aloe vera extracts increased the viscosity of saliva substitutes. the addition of propolis for 2.5 or 5 wt% to saliva substitutes increased mineral apatite precipitation and tubule occlusion. To conclude, the saliva substitute containing propolis extract demonstrated superior remineralizing actions compared with those containing only aloe vera extract.

PMID:38776324 | DOI:10.1371/journal.pone.0304156

Skin Res Technol. 2024 May;30(5):e13749. doi: 10.1111/srt.13749.

ABSTRACT

BACKGROUND: Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.

MATERIALS AND METHODS: Four databases were searched from the database’s creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta-analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk-of-bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs).

RESULTS: In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta-regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo.

CONCLUSION: 300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.

PMID:38776128 | DOI:10.1111/srt.13749

JAMA Netw Open. 2024 May 1;7(5):e2412929. doi: 10.1001/jamanetworkopen.2024.12929.

NO ABSTRACT

PMID:38776088 | DOI:10.1001/jamanetworkopen.2024.12929

JAMA Netw Open. 2024 May 1;7(5):e2412946. doi: 10.1001/jamanetworkopen.2024.12946.

NO ABSTRACT

PMID:38776086 | DOI:10.1001/jamanetworkopen.2024.12946