Tag: nevin manimala

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

JAMA Netw Open. 2024 May 1;7(5):e2411322. doi: 10.1001/jamanetworkopen.2024.11322.

ABSTRACT

IMPORTANCE: Concerns about the mental health of youths going through gender identity transitions have received increased attention. There is a need for empirical evidence to understand how transitions in self-reported gender identity are associated with mental health.

OBJECTIVE: To examine whether and how often youths changed self-reported gender identities in a longitudinal sample of sexual and gender minority (SGM) youths, and whether trajectories of gender identity were associated with depressive symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 4 waves (every 9 months) of a longitudinal community-based study collected in 2 large cities in the US (1 in the Northeast and 1 in the Southwest) between November 2011 and June 2015. Eligible participants included youths who self-identified as SGM from community-based agencies and college groups for SGM youths. Data analysis occurred from September 2022 to June 2023.

EXPOSURE: Gender identity trajectories and gender identity variability.

MAIN OUTCOMES AND MEASURES: The Beck Depression Inventory for Youth (BDI-Y) assessed depressive symptoms. Gender identity variability was measured as the number of times participants’ gender identity changed. Hierarchical linear models investigated gender identity trajectories and whether gender identity variability was associated with depressive symptoms over time.

RESULTS: Among the 366 SGM youths included in the study (mean [SD] age, 18.61 [1.71] years; 181 [49.4%] assigned male at birth and 185 [50.6%] assigned female at birth), 4 gender identity trajectory groups were identified: (1) cisgender across all waves (274 participants ), (2) transgender or gender diverse (TGD) across all waves (32 participants), (3) initially cisgender but TGD by wave 4 (ie, cisgender to TGD [28 participants]), and (4) initially TGD but cisgender by wave 4 (ie, TGD to cisgender [32 participants]). One in 5 youths (18.3%) reported a different gender identity over a period of approximately 3.5 years; 28 youths varied gender identity more than twice. The cisgender to TGD group reported higher levels of depression compared with the cisgender group at baseline (Β = 4.66; SE = 2.10; P = .03), but there was no statistical difference once exposure to lesbian, gay, bisexual, and transgender violence was taken into account (Β = 3.31; SE = 2.36; P = .16). Gender identity variability was not associated with within-person change in depressive symptoms (Β = 0.23; SE = 0.74; P = .75) or the level of depressive symptoms (Β = 2.43; SE = 2.51; P = .33).

CONCLUSIONS: These findings suggest that gender identity can evolve among SGM youths across time and that changes in gender identity are not associated with changes in depressive symptoms. Further longitudinal work should explore gender identity variability and adolescent and adult health.

PMID:38776085 | DOI:10.1001/jamanetworkopen.2024.11322

JAMA Netw Open. 2024 May 1;7(5):e2412535. doi: 10.1001/jamanetworkopen.2024.12535.

ABSTRACT

IMPORTANCE: Reducing the pretrial detention population has been a cornerstone of movements to end mass incarceration. Across many US cities, there are ongoing public debates on policies that would end pretrial detention due to the inability to afford bail, with some raising concerns that doing so would increase community violence.

OBJECTIVE: To evaluate changes in firearm violence after New Jersey’s 2017 bail reform policy that eliminated financial barriers to avoiding pretrial detention.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study used synthetic control methods to examine changes in firearm mortality and combined fatal and nonfatal shootings in New Jersey (2014-2019). New Jersey was chosen because it was one of the first states to systematically implement cash bail reform. Outcomes in New Jersey were compared with a weighted combination of 36 states that did not implement any kind of reform to pretrial detention during the study period. Data were analyzed from April 2023 to March 2024.

EXPOSURE: Implementation of New Jersey’s cash bail reform law in 2017.

MAIN OUTCOMES AND MEASURES: Quarterly rates of fatal and nonfatal firearm assault injuries and firearm self-harm injuries per 100 000 people.

RESULTS: Although New Jersey’s pretrial detention population dramatically decreased under bail reform, the study did not find evidence of increases in overall firearm mortality (average treatment effect on the treated, -0.26 deaths per 100 000) or gun violence (average treatment effect on the treated, -0.24 deaths per 100 000), or within racialized groups during the postpolicy period.

CONCLUSIONS AND RELEVANCE: Incarceration and gun violence are major public health problems impacting racially and economically marginalized groups. Cash bail reform may be an important tool for reducing pretrial detention and advancing health equity without exacerbating community violence.

PMID:38776084 | DOI:10.1001/jamanetworkopen.2024.12535