Category: Nevin Manimala

J Comput Biol. 2023 Mar 10. doi: 10.1089/cmb.2022.0201. Online ahead of print.

ABSTRACT

Ordinary differential equations (ODEs) are widely used for elucidating dynamic processes in various fields. One of the applications of ODEs is to describe dynamics of gene regulatory networks (GRNs), which is a critical step in understanding disease mechanisms. However, estimation of ODE models for GRNs is challenging because of inflexibility of the model and noisy data with complex error structures such as heteroscedasticity, correlations between genes, and time dependency. In addition, either a likelihood or Bayesian approach is commonly used for estimation of ODE models, but both approaches have benefits and drawbacks in their own right. Data cloning is a maximum likelihood (ML) estimation method through the Bayesian framework. Since it works in the Bayesian framework, it is free from local optimum problems that are common drawbacks of ML methods. Also, its inference is invariant for the selection of prior distributions, which is a major issue in Bayesian methods. This study proposes an estimation method of ODE models for GRNs through data cloning. The proposed method is demonstrated through simulation and it is applied to real gene expression time-course data.

PMID:36898058 | DOI:10.1089/cmb.2022.0201

Am J Drug Alcohol Abuse. 2023 Mar 10:1-12. doi: 10.1080/00952990.2023.2170806. Online ahead of print.

ABSTRACT

Background: Previous research conducted among Latino/a immigrants has shown the underlying effect that exposure to stress after immigrating to the U.S. (i.e. health access, racial/ethnic discrimination, and language barriers) has on alcohol use patterns. However, given the demographic shifts in recent immigrants, understanding the influence of stress before (i.e. poverty, healthcare, and educational opportunities) and after immigration on their alcohol use (i.e. alcohol consumption and drinking behaviors in the past 12 months) in the context of migration and traditional gender roles is warranted.Objectives: To examine the (a) cumulative effects of pre- to post-immigration stress, (b) respective moderating effects of traditional gender roles, and (c) forced migration on alcohol use for men and women.Methods: Hierarchical multiple regression and moderation analyses were conducted on a cross-sectional sample of 529 (N = 268 men, N = 261 women) adult (18-34 years) from recent Latino/a immigrants in South Florida.Results: Gender had a statistically significant difference on alcohol use, (F 527) = 18.68, p < .001, with men (p = 4.36 ± SE =.22) reporting higher alcohol use than women (p = 3.08 ± SE =.20). Post-immigration stress (β = .12, p = .03) but not pre-migration stress had a statistically significant association with alcohol use. There is no interaction effect by traditional gender roles and forced migration on the associations between pre- to post-immigration stress and alcohol use.Conclusion: Results suggest that post-immigration stress may be a reasonable intervention target to mitigate alcohol use among recent Latino/a immigrants, particularly among men.

PMID:36898052 | DOI:10.1080/00952990.2023.2170806

J Pediatr Hematol Oncol. 2023 Mar 3. doi: 10.1097/MPH.0000000000002651. Online ahead of print.

ABSTRACT

PURPOSE: Survivorship care plans (SCPs) have been instrumental in aiding transition from cancer treatment to survivorship care, which contains the diagnosis, treatment, potential late effects, and recommended follow-up. There has been paucity of research on its efficacy and lack of guidelines on development and delivery of SCPs. The Next Steps Survivorship Clinic at Children’s Wisconsin uses a Survivorship Healthcare Passport (SHP), a SCP pocket-sized card. This study aims to improve understanding of patient and parent use of the SHP at a single institution.

MATERIALS AND METHODS: An electronic survey was distributed to cancer survivors (14 to 28 y old) and parents/guardians who received the SCP. Data was analyzed with descriptive and correlation statistics.

RESULTS: Older survivors were reliable in carrying their SHP, and endorsed greater confidence in understanding its contents leading to a notion of improved ability to coordinate care. Younger survivors tend to rely on their parents. A preference for a smartphone application as another platform was noted.

CONCLUSIONS: This form of SCP has shown to benefit older survivors which directly impacts the notion of efficacy in care coordination.

IMPLICATION FOR CANCER SURVIVORS: Providing easy-to-access information may encourage survivors to advocate for their health and to facilitate transition of care.

PMID:36898042 | DOI:10.1097/MPH.0000000000002651

Prim Care Companion CNS Disord. 2023 Feb 28;25(1):22m03334. doi: 10.4088/PCC.22m03334.

ABSTRACT

Objective: To determine the prevalence of bedtime procrastination (BtP) among Indian university students and to evaluate the performance of the Bedtime Procrastination Scale (BPS).

Methods: The BPS (scoring range, 9-45), with separate, additional questions related to sleep and influences thereon, was administered to all on-campus graduate and postgraduate students attending Navrachana University, Gujarat, India. The variable of regular sleep habits was defined as a BPS total score of 9-18 and BtP as a BPS total of 36-45. The BPS was examined using factor analysis. The study was conducted from November 2021 to December 2021.

Results: Completed forms were received from 560 of 567 eligible students. The mean BPS total score was 29.1. BPS total scores did not differ significantly between males and females. Few students (n = 54, 9.6%) had study-defined regular sleep habits. One-fifth of the sample (20.2%) had study-defined BtP. Higher BtP total scores showed a small but statistically significant correlation with daytime tiredness (r = 0.26). Factor analysis of the BPS yielded a 2-factor solution that explained 49.3% of the variance in the data. The latent variables appeared to represent “Going to bed late” and “Going to bed on time.” Potential problems, not previously discussed in the literature, were identified based on the manner in which BPS items were presented and scored.

Conclusions: Few university students have regular sleep habits. BtP is present in a sufficiently large enough proportion of students to be of health concern. The BPS is likely to require modifications for future use.

PMID:36898024 | DOI:10.4088/PCC.22m03334

Am J Hosp Palliat Care. 2023 Mar 10:10499091231163269. doi: 10.1177/10499091231163269. Online ahead of print.

ABSTRACT

Introduction: This study describes the end-of-life (EOL) care planning and bereavement practices among adult day services centers (ADSC) when an ADSC participant is dying or has died. Methods: Data are from the 2018 National Study of Long-term Care Providers’ biennial survey of ADSCs. Respondents were asked about the following 4 practices: 1) honoring the deceased in some public way in this center; 2) offering bereavement services to staff and participants; 3) documenting in the care plan what is important to the individual at the end of life (EOL), such as the presence of family or religious or cultural practices; and 4) discussing spiritual needs at care planning conferences. ADSC characteristics included US Census region, metropolitan statistical area status, Medicaid authorization, electronic health records (EHR) use, for-profit status, employment of aides, services provision, and model type. Results: About 50% to 30% of ADSCs offered the EOL care planning or bereavement services. Honoring the deceased was the most common practice (53%), followed by bereavement services (37%), discussing spiritual needs (29%), and documenting what is important at EOL (28%). Fewer ADSCs in the West had EOL practices relative to the other regions. The EOL planning and bereavement practices were offered more often in ADSCs that used EHRs, accepted Medicaid, employed an aide, provided nursing, hospice, and palliative care services, and were categorized as medical models, compared with ADSCs without these characteristics. Conclusion: These results highlight the importance of understanding how ADSCs provide EOL and bereavement care to participants who are near EOL.

PMID:36898004 | DOI:10.1177/10499091231163269

J Phys Chem B. 2023 Mar 10. doi: 10.1021/acs.jpcb.2c08915. Online ahead of print.

ABSTRACT

The carbonyl stretching modes have been widely used in linear and two-dimensional infrared (IR) spectroscopy to probe the conformation, interaction, and biological functions of nucleic acids. However, due to their universal appearance in nucleobases, the IR absorption bands of nucleic acids are often highly congested in the 1600-1800 cm^-1 region. Following the fruitful applications in proteins, ¹³C isotope labels have been introduced to the IR measurements of oligonucleotides to reveal their site-specific structural fluctuations and hydrogen bonding conditions. In this work, we combine recently developed frequency and coupling maps to develop a theoretical strategy that models the IR spectra of oligonucleotides with ¹³C labels directly from molecular dynamics simulations. We apply the theoretical method to nucleoside 5′-monophosphates and DNA double helices and demonstrate how elements of the vibrational Hamiltonian determine the spectral features and their changes upon isotope labeling. Using the double helices as examples, we show that the calculated IR spectra are in good agreement with experiments and the ¹³C isotope labeling technique can potentially be applied to characterize the stacking configurations and secondary structures of nucleic acids.

PMID:36898003 | DOI:10.1021/acs.jpcb.2c08915

Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2214977120. doi: 10.1073/pnas.2214977120. Epub 2023 Mar 10.

ABSTRACT

Adaptation in protein-coding sequences can be detected from multiple sequence alignments across species or alternatively by leveraging polymorphism data within a population. Across species, quantification of the adaptive rate relies on phylogenetic codon models, classically formulated in terms of the ratio of nonsynonymous over synonymous substitution rates. Evidence of an accelerated nonsynonymous substitution rate is considered a signature of pervasive adaptation. However, because of the background of purifying selection, these models are potentially limited in their sensitivity. Recent developments have led to more sophisticated mutation-selection codon models aimed at making a more detailed quantitative assessment of the interplay between mutation, purifying, and positive selection. In this study, we conducted a large-scale exome-wide analysis of placental mammals with mutation-selection models, assessing their performance at detecting proteins and sites under adaptation. Importantly, mutation-selection codon models are based on a population-genetic formalism and thus are directly comparable to the McDonald and Kreitman test at the population level to quantify adaptation. Taking advantage of this relationship between phylogenetic and population genetics analyses, we integrated divergence and polymorphism data across the entire exome for 29 populations across 7 genera and showed that proteins and sites detected to be under adaptation at the phylogenetic scale are also under adaptation at the population-genetic scale. Altogether, our exome-wide analysis shows that phylogenetic mutation-selection codon models and the population-genetic test of adaptation can be reconciled and are congruent, paving the way for integrative models and analyses across individuals and populations.

PMID:36897968 | DOI:10.1073/pnas.2214977120

Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2122352120. doi: 10.1073/pnas.2122352120. Epub 2023 Mar 10.

ABSTRACT

A crucial challenge in medicine is choosing which drug (or combination) will be the most advantageous for a particular patient. Usually, drug response rates differ substantially, and the reasons for this response unpredictability remain ambiguous. Consequently, it is central to classify features that contribute to the observed drug response variability. Pancreatic cancer is one of the deadliest cancers with limited therapeutic achievements due to the massive presence of stroma that generates an environment that enables tumor growth, metastasis, and drug resistance. To understand the cancer-stroma cross talk within the tumor microenvironment and to develop personalized adjuvant therapies, there is a necessity for effective approaches that offer measurable data to monitor the effect of drugs at the single-cell level. Here, we develop a computational approach, based on cell imaging, that quantifies the cellular cross talk between pancreatic tumor cells (L3.6pl or AsPC1) and pancreatic stellate cells (PSCs), coordinating their kinetics in presence of the chemotherapeutic agent gemcitabine. We report significant heterogeneity in the organization of cellular interactions in response to the drug. For L3.6pl cells, gemcitabine sensibly decreases stroma-stroma interactions but increases stroma-cancer interactions, overall enhancing motility and crowding. In the AsPC1 case, gemcitabine promotes the interactions among tumor cells, but it does not affect stroma-cancer interplay, possibly suggesting a milder effect of the drug on cell dynamics.

PMID:36897966 | DOI:10.1073/pnas.2122352120

Sci Adv. 2023 Mar 10;9(10):eabo1638. doi: 10.1126/sciadv.abo1638. Epub 2023 Mar 10.

ABSTRACT

Increases in concurrent climate extremes in different parts of the world threaten the ecosystem and our society. However, spatial patterns of these extremes and their past and future changes remain unclear. Here, we develop a statistical framework to test for spatial dependence and show widespread dependence of temperature and precipitation extremes in observations and model simulations, with more frequent than expected concurrence of extremes around the world. Historical anthropogenic forcing has strengthened the concurrence of temperature extremes over 56% of 946 global paired regions, particularly in the tropics, but has not yet significantly affected concurrent precipitation extremes during 1901-2020. The future high-emissions pathway of SSP585 will substantially amplify the concurrence strength, intensity, and spatial extent for both temperature and precipitation extremes, especially over tropical and boreal regions, while the mitigation pathway of SSP126 can ameliorate the increase in concurrent climate extremes for these high-risk regions. Our findings will inform adaptation strategies to alleviate the impact of future climate extremes.

PMID:36897946 | DOI:10.1126/sciadv.abo1638

PLoS One. 2023 Mar 10;18(3):e0282730. doi: 10.1371/journal.pone.0282730. eCollection 2023.

ABSTRACT

BACKGROUND: Research into mood and emotion has often depended on slow and subjective self-report, highlighting a need for rapid, accurate, and objective assessment tools.

METHODS: To address this gap, we developed a method using digital image speckle correlation (DISC), which tracks subtle changes in facial expressions invisible to the naked eye, to assess emotions in real-time. We presented ten participants with visual stimuli triggering neutral, happy, and sad emotions and quantified their associated facial responses via detailed DISC analysis.

RESULTS: We identified key alterations in facial expression (facial maps) that reliably signal changes in mood state across all individuals based on these data. Furthermore, principal component analysis of these facial maps identified regions associated with happy and sad emotions. Compared with commercial deep learning solutions that use individual images to detect facial expressions and classify emotions, such as Amazon Rekognition, our DISC-based classifiers utilize frame-to-frame changes. Our data show that DISC-based classifiers deliver substantially better predictions, and they are inherently free of racial or gender bias.

LIMITATIONS: Our sample size was limited, and participants were aware their faces were recorded on video. Despite this, our results remained consistent across individuals.

CONCLUSIONS: We demonstrate that DISC-based facial analysis can be used to reliably identify an individual’s emotion and may provide a robust and economic modality for real-time, noninvasive clinical monitoring in the future.

PMID:36897921 | DOI:10.1371/journal.pone.0282730