Tag: pubmed

Bioinformatics. 2022 May 16:btac325. doi: 10.1093/bioinformatics/btac325. Online ahead of print.

ABSTRACT

MOTIVATION: Interactions between peptide fragments and protein receptors are vital to cell function yet difficult to experimentally determine in structural details of. As such, many computational methods have been developed to aid in peptide-protein docking or structure prediction. One such method is Rosetta FlexPepDock which consistently refines coarse peptide-protein models into sub-Ångström precision using Monte-Carlo simulations and statistical potentials. Deep learning has recently seen increased use in protein structure prediction, with graph neural networks used for protein model quality assessment.

RESULTS: Here, we introduce a graph neural network, InterPepScore, as an additional scoring term to complement and improve the Rosetta FlexPepDock refinement protocol. InterPepScore is trained on simulation trajectories from FlexPepDock refinement starting from thousands of peptide-protein complexes generated by a wide variety of docking schemes. The addition of InterPepScore into the refinement protocol consistently improves the quality of models created, and on an independent benchmark on 109 peptide-protein complexes its inclusion results in an increase in the number of complexes for which the top-scoring model had a DockQ-score of 0.49 (Medium quality) or better from 14.8% to 26.1%.

AVAILABILITY: InterPepScore is available online at http://wallnerlab.org/InterPepScore.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35575349 | DOI:10.1093/bioinformatics/btac325

ACS Macro Lett. 2022 Apr 19;11(4):580-587. doi: 10.1021/acsmacrolett.2c00046. Epub 2022 Apr 7.

ABSTRACT

Overexpression of epidermal growth factor receptor (EGFR) is observed in multiple cancers such as colorectal, lung, and cervical solid tumors. Regulating the EGFR expression is an efficient strategy to manage these malignancies, and it can be achieved by using short interfering RNA (siRNA). Cell-penetrating peptides (CPPs) demonstrated an excellent capability to enhance the cellular uptake of siRNA, but high knockdown efficiencies have not been achieved due to endosomal entrapment. In this work, Schiff’s base reaction was used to modify a block {P[LAEMA(2-lactobionamidoethyl methacrylamide)₃₇]-b-P[FPMA(4-formyl phenyl methacrylate)₂–st-DMA(N,N-dimethylacrylamide)₂], P2} and two statistical [P(LAEMA₂₃–st-FPMA₃) (P3) and P(LAEMA₂₅–st-FPMA₂–st-DMA₂) (P4)] aldehyde-based and galactose-based polymers, prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerization. An arginine-rich peptide (ARP, KRRKRRRRRK) was used as a cell-penetrating peptide (CPP) and conjugated to the polymers via a Schiff base reaction. The resulting glycopolymer-peptide conjugates were utilized to condense the siRNA to prepare polyplexes with multivalent CPPs (MCPPs, a nanoparticle with multiple copies of the CPP) to enhance the endosomal escape. The polyplexes have different surface properties as determined by the architecture of polymers and the insertion of dimethyl amide moieties. The enhancement of cellular internalization of ARP was observed by labeling the polyplexes with fluorescein isothiocyanate (FITC)-siRNA showing a localization of polyplexes in the cytoplasm of a HeLa (cervical cancer) cell line. In the in vitro EFGR silencing study, the statistical glycopolymer-peptide (P3-P) polyplexes had superior EGFR silencing efficiency in comparison with the other polymers that were studied. Furthermore, P3-P polyplexes led to less off-targeting silencing than lipofectamine 3000. These encouraging results confirmed the potency of decorating galactose-based polymers with CPP, like ARP for their application in siRNA delivery and management of cervical carcinomas.

PMID:35575337 | DOI:10.1021/acsmacrolett.2c00046

ACS Macro Lett. 2022 Apr 19;11(4):498-503. doi: 10.1021/acsmacrolett.1c00776. Epub 2022 Mar 22.

ABSTRACT

Polymers that exhibit a lower critical solution temperature (LCST) have been of great interest for various biological applications such as drug or gene delivery, controlled release systems, and biosensing. Tuning the LCST behavior through control over polymer composition (e.g., upon copolymerization of monomers with different hydrophobicity) is a widely used method, as the phase transition is greatly affected by the hydrophilic/hydrophobic balance of the copolymers. However, the lack of a general method that relates copolymer hydrophobicity to their temperature response leads to exhaustive experiments when seeking to obtain polymers with desired properties. This is particularly challenging when the target copolymers are comprised of monomers that individually form nonresponsive homopolymers, that is, only when copolymerized do they display thermoresponsive behavior. In this study, we sought to develop a predictive relationship between polymer hydrophobicity and cloud point temperature (T_CP). A series of statistical copolymers were synthesized based on hydrophilic N,N-dimethyl acrylamide (DMA) and hydrophobic alkyl acrylate monomers, and their hydrophobicity was compared using surface area-normalized octanol/water partition coefficients (Log P_oct/SA). Interestingly, a correlation between the Log P_oct/SA of the copolymers and their T_CPs was observed for the P(DMA-co-RA) copolymers, which allowed T_CP prediction of a demonstrative copolymer P(DMA-co-MMA). These results highlight the strong potential of this computational tool to improve the rational design of copolymers with desired temperature responses prior to synthesis.

PMID:35575334 | DOI:10.1021/acsmacrolett.1c00776

Palliat Support Care. 2022 Apr;20(2):264-274. doi: 10.1017/S1478951521001279.

ABSTRACT

BACKGROUND: The significance of spiritual care needs among chronic diseases patients has been emphasized across countries and cultures in many studies. However, there were few studies on spiritual care needs among elderly patients with moderate-to-severe chronic heart failure (CHF) in China.

OBJECTIVE: To investigate spiritual care needs and associated influencing factors among elderly patients with moderate-to-severe CHF, and to examine the relationships among spiritual care needs, self-perceived burden, symptom management self-efficacy, and perceived social support.

METHODS: A cross-sectional design was implemented, and the STROBE Checklist was used to report the study. A convenience sample of 474 elderly patients with moderate-to-severe CHF were selected from seven hospitals in Tianjin, China. The sociodemographic characteristics questionnaire, the Spiritual Needs Questionnaire Scale, the Self-Perceived Burden Scale, the Self-efficacy for Symptom Management Scale, and the Perceived Social Support Scale were used. Descriptive statistics, univariate, multiple linear regression, and Pearson’s correlation analysis were used to analyze data.

RESULTS: The total score of spiritual care needs among 474 elderly patients with moderate-to-severe CHF was 37.95 ± 14.71, which was moderate. Religious belief, educational background, self-perceived burden, symptom management self-efficacy, and perceived social support were the main factors affecting spiritual care needs, and spiritual care needs were negatively correlated with self-perceived burden (r = -0.637, p < 0.01) and positively correlated with symptom management self-efficacy (r = 0.802, p < 0.01) and social support (r = 0.717, p < 0.01).

SIGNIFICANCE OF RESULTS: The spiritual care needs of elderly patients with moderate-to-severe CHF were moderate, which were influenced by five factors. It is suggested that clinical nurses, families, and society should take targeted spiritual care measures to improve patients’ symptom management self-efficacy and perceived social support from many aspects, and reduce self-perceived burden to meet their spiritual care needs and improve the quality and satisfaction of spiritual care in nursing practice.

PMID:35574915 | DOI:10.1017/S1478951521001279

J Health Care Poor Underserved. 2022;33(2):790-805. doi: 10.1353/hpu.2022.0064.

ABSTRACT

OBJECTIVES: Determine if United States graduates of the Latin American Medical School in Cuba: 1) provide primary health care to disadvantaged populations; 2) complete licensing exams and obtain residencies; and 3) accrue additional debt during their medical education.

METHODS: A Qualtrics secure web-based survey was provided to 158 graduates via email, completed anonymously. Responses were compiled and descriptive statistics generated.

RESULTS: Fifty-six valid surveys were returned, for a response rate of 35.4%. Chi-square analysis showed no statistically significant differences between survey respondents and the sampling frame. Most graduates are people of color; 68% work in clinical medicine; of these, 90% are in primary care, with 100% serving disadvantaged populations. Most accrued no further educational loan debt.

CONCLUSIONS: United States graduates of the Latin American Medical School work in primary care with disadvantaged populations. Graduates accrue little additional student loan debt.

PMID:35574877 | DOI:10.1353/hpu.2022.0064

J Health Care Poor Underserved. 2022;33(2):806-818. doi: 10.1353/hpu.2022.0065.

ABSTRACT

OBJECTIVE: We examined the prevalence and correlates of interest in receiving HIV pre-exposure prophylaxis (PrEP) in Latinx migrants at high-risk of HIV infection in Tijuana, Mexico, a migrant sending/receiving community bordering California.

METHODS: In 2016, 870 HIV-seronegative biologically male Latinx migrants ages 18 and older responded to interviewer-administered surveys. Univariate statistics and multivariable analyses were estimated.

RESULTS: In multivariable logistic regression analyses, emerging adults (18-24 years) were significantly less likely than participants ages 45 and older to be interested in PrEP (AOR: 0.35; 95% CI: 0.13, 0.89). Those who ever had sex with another male (AOR: 1.78; 95% CI: 1.13, 2.80), and who recently used illicit drugs (AOR: 1.74, 95% 1.09, 2.75) were significantly more likely to be interested in receiving PrEP.

CONCLUSIONS: Provision of PrEP to migrant males at high-risk of HIV is needed. In Mexico, expanding access to federal health insurance and reducing the costs of PrEP are urgently needed.

PMID:35574878 | DOI:10.1353/hpu.2022.0065

J Health Care Poor Underserved. 2022;33(2):702-713. doi: 10.1353/hpu.2022.0057.

ABSTRACT

Existing research examines the effectiveness of medical home initiatives for Children with medical complexity (CMC), but not their siblings. This research sheds light on the care these siblings receive in the medical home. We assessed the preventative care status and medical home use of the siblings of CMC in four academic pediatric medical homes. We conducted an 18-month retrospective chart review of 236 siblings of CMC and 230 nonsiblings, matched by age and medical home. We found a statistically significant difference in the medical home use of siblings of CMC compared with non-siblings. They are not up to date on well-child care visits and are much less likely to be identified as children with special health care needs (CSHCN). This may lead to omission from registries and fewer interventions for outreach and support. Further attention is needed to develop methods that ensure appropriate care for this vulnerable population.

PMID:35574870 | DOI:10.1353/hpu.2022.0057

J Health Care Poor Underserved. 2022;33(2):580-589. doi: 10.1353/hpu.2022.0048.

ABSTRACT

Medical-legal partnerships (MLPs) add legal professionals, trained specifically to tackle health-related social needs (HRSN), to the health care team. We evaluated the impact on health outcomes and health care utilization of a MLP housed in a large federally qualified health center in Colorado (MLP-CO). Clients screened for I-HELP (Income, Housing, Employment, Legal status, Personal stability) needs were surveyed at baseline and six months post-enrollment. Reasons for legal aid were legal immigration status (46.5%), income (30.8%), personal/family stability (14.8%), housing (4.8%), and education (1.2%). Overall, 61.4% attributed great/moderate improvements in their health care experience to the MLP-CO. Statistically significant improvements were noted for days with poor physical/mental health, and feelings of stress/worry. There was a reduction in emergency department visits, hospitalization days, and missed appointments, but only the latter was statistically significant. In conclusion, MLPs are a promising innovation to achieve the Institute for Healthcare Improvement’s quadruple aim.

PMID:35574861 | DOI:10.1353/hpu.2022.0048

Stat Med. 2022 May 16. doi: 10.1002/sim.9428. Online ahead of print.

ABSTRACT

In research synthesis, publication bias (PB) refers to the phenomenon that the publication of a study is associated with the direction and statistical significance of its results. Consequently, it may lead to biased (commonly optimistic) estimates of treatment effects. Visualization tools such as funnel plots have been widely used to investigate PB in univariate meta-analyses. The trim and fill procedure is a nonparametric method to identify and adjust for PB. It is popular among applied scientists due to its simplicity. However, most visualization tools and PB correction methods focus on univariate outcomes. For a meta-analysis with multiple outcomes, the conventional univariate trim and fill method can only account for different outcomes separately and thus may lead to inconsistent conclusions. In this article, we propose a bivariate trim and fill procedure to simultaneously account for PB in the presence of two outcomes that are possibly associated. Based on a recently developed galaxy plot for bivariate meta-analysis, the proposed procedure uses a data-driven imputation algorithm to detect and adjust PB. The method relies on the symmetry of the galaxy plot and assumes that some studies are suppressed based on a linear combination of outcomes. The method projects bivariate outcomes along a particular direction, uses the univariate trim and fill method to estimate the number of trimmed and filled studies, and yields consistent conclusions about PB. The proposed approach is validated using simulated data and is applied to a meta-analysis of the efficacy and safety of antidepressant drugs.

PMID:35574857 | DOI:10.1002/sim.9428

J Health Care Poor Underserved. 2022;33(2):571-579. doi: 10.1353/hpu.2022.0047.

ABSTRACT

Cardiovascular disease (CVD) is a leading cause of mortality among U.S. adults, especially low-income and uninsured adults. Non-Hispanic Black adults, who are overrepresented among low-income and uninsured populations, are disproportionately burdened by CVD mortality compared with non-Hispanic White adults. Medicaid expansion is associated with improved insurance coverage and access to care among low-income adults as well as reduced CVD mortality. It is unclear whether Medicaid expansion has reduced the Black-White disparity in CVD mortality. This study estimated a difference-in-differences model to compare changes in county-level CVD mortality ratios between expansion and non-expansion states. Findings indicate that Medicaid expansion is not associated with a statistically significant reduction in Black-White disparities in CVD mortality (β = -.039; p =.30). In conclusion, Medicaid expansion may be associated with improved health outcomes and access to care overall; however, it is insufficient to overcome other (i.e., social and economic) drivers of racial/ethnic disparities in CVD mortality.

PMID:35574860 | DOI:10.1353/hpu.2022.0047