Category: Statistics

Dev Psychobiol. 2024 Apr;66(3):e22479. doi: 10.1002/dev.22479.

ABSTRACT

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of this review is dedicated to pharmacological interventions and epigenetic editing as tools for studying the causal role of epigenetic mechanisms in the development of physiological and behavioral profiles. A special section of the manuscript will discuss the translational potential of the discussed research.

PMID:38470450 | DOI:10.1002/dev.22479

J Vet Dent. 2024 Mar 12:8987564241232862. doi: 10.1177/08987564241232862. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the effects of Coriandrum sativum L. (CSL) seed extract on gingival levels of antioxidant enzymes, pro-inflammatory cytokines and on alveolar bone and attachment levels after experimental periodontitis induction in rats and compare it with low-dose doxycycline (LDD). Forty adult male Wistar Albino rats were divided randomly into 5 groups as follows: 1 = periodontally healthy (control); 2 = periodontitis; 3 = periodontitis + CSL (32 mg/kg); 4 = periodontitis + CSL (200 mg/kg); and 5 = periodontitis + LDD (6 mg/kg). Gingival superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) levels were evaluated by enzyme-linked immunosorbent assay. The presence of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1βeta (IL-1β) immunoreactivity was detected immunohistochemically. Alveolar bone area in the furcation space (ABA), alveolar bone loss (ABL), and attachment loss (AL) were evaluated histomorphometrically. The SOD level was lower in group 5 than in groups 2, 3, and 4. The IL-1β level was highest in group 4. The TNF-α level was statistically higher in groups 2 and 4 than in groups 1, 3, and 5. The IL-6 level was highest in group 4. Its level was higher in groups 2 and 3 than in group 5. ABA was less in groups 2, 3, and 4 compared to groups 1 and 5. ABL was less in group 5 than in groups 2, 3, and 4. AL was greater in group 4 than in group 5. The use of 200 mg/kg CSL showed a pro-inflammatory effect and IL-1β and TNF-α levels decreased after 32 mg/kg CSL application in the treatment of periodontitis.

PMID:38470443 | DOI:10.1177/08987564241232862

JAMA Netw Open. 2024 Mar 4;7(3):e240555. doi: 10.1001/jamanetworkopen.2024.0555.

ABSTRACT

IMPORTANCE: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives.

OBJECTIVE: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children’s hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded.

EXPOSURE: Any opioid exposure and methadone treatment.

MAIN OUTCOMES AND MEASURES: Regional and institutional variations in opioid exposure.

RESULTS: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

PMID:38470421 | DOI:10.1001/jamanetworkopen.2024.0555

JAMA Netw Open. 2024 Mar 4;7(3):e241958. doi: 10.1001/jamanetworkopen.2024.1958.

ABSTRACT

IMPORTANCE: COVID-19 prompted rapid development of scarce resource allocation (SRA) policies to be implemented if demand eclipsed health systems’ ability to provide critical care. While SRA policies follow general ethical frameworks, understanding priorities of those affected by policies and/or tasked with implementing them is critical.

OBJECTIVE: To evaluate whether community members and health care profesionals (HCP) agree with SRA protocols at the University of California (UC).

DESIGN, SETTING, AND PARTICIPANTS: This survey study used social media and community-partnered engagement to recruit participants to a web-based survey open to all participants aged older than 18 years who wished to enroll. This study was fielded between May and September 2020 and queried participants’ values and preferences on draft SRA policy tenets. Participants were also encouraged to forward the survey to their networks for snowball sampling. Data were analyzed from July 2020 to January 2024.

MAIN OUTCOMES AND MEASURES: Survey items assessed values and preferences, graded on Likert scales. Agreement was tabulated as difference in Likert points between expressed opinion and policy tenets. Descriptive statistics were tested for significance by HCP status. Free text responses were analyzed using applied rapid qualitative analysis.

RESULTS: A total of 1545 participants aged older than 18 years (mean [SD] age 49 [16] years; 1149 female participants [74%], 478 health care practitioners [30%]) provided data on SRA values and preferences. Agreement with UC SRA policy as drafted was moderately high among respondents, ranging from 67% to 83% across domains. Higher agreement with the interim policy was observed for laypersons across all domains except health-related factors. HCPs agreed more strongly on average that resources should not be allocated to those less likely to survive (HCP mean, 3.70; 95% CI, 3.16-3.59; vs layperson mean, 3.38; 95% CI, 3.17-3.59; P = .002), and were more in favor of reallocating life support from patients less likely to those more likely to survive (HCP mean, 6.41; 95% CI, 6.15-6.67; vs layperson mean, 5.40; 95% CI, 5.23-5.58; P < .001). Transparency and trust building themes were common in free text responses and highly rated on scaled items.

CONCLUSIONS AND RELEVANCE: This survey of SRA policy values found moderate agreement with fundamental principles of such policies. Engagement with communities affected by SRA policy should continue in iterative refinement in preparation for future crises.

PMID:38470416 | DOI:10.1001/jamanetworkopen.2024.1958

J Chem Theory Comput. 2024 Mar 12. doi: 10.1021/acs.jctc.3c01381. Online ahead of print.

ABSTRACT

The determination of the solvation free energy of ions and molecules holds profound importance across a spectrum of applications spanning chemistry, biology, energy storage, and the environment. Molecular dynamics simulations are powerful tools for computing this critical parameter. Nevertheless, the accurate and efficient calculation of the solvation free energy becomes a formidable endeavor when dealing with complex systems characterized by potent Coulombic interactions and sluggish ion dynamics and, consequently, slow transition across various metastable states. In the present study, we expose limitations stemming from the conventional calculation of the statistical inefficiency g in the thermodynamic integration method, a factor that can hinder the determination of convergence of the solvation free energy and its associated uncertainty. Instead, we propose a robust scheme based on Gelman-Rubin convergence diagnostics. We leverage this improved estimation of uncertainties to introduce an innovative accelerated thermodynamic integration method based on the Gaussian Process regression. This methodology is applied to the calculation of the solvation free energy of trivalent rare-earth elements immersed in ionic liquids, a scenario in which the aforementioned challenges render standard approaches ineffective. The proposed method proves to be effective in computing solvation free energy in situations where traditional thermodynamic integration methods fall short.

PMID:38470415 | DOI:10.1021/acs.jctc.3c01381

Cancer. 2024 Mar 12. doi: 10.1002/cncr.35276. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to estimate the event-free survival (EFS) of children and young adults with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) treated in nonrandomized phase 2 studies conducted by the Children’s Oncology Group (COG) and predecessor groups to establish a benchmark EFS for future phase 2 NRSTS trials evaluating the activity of novel agents.

METHODS: A retrospective analysis of patients with recurrent or refractory NRSTS prospectively enrolled in nonrandomized phase 2 COG and predecessor group trials between 1994 and 2015 was conducted. EFS was defined as disease progression/relapse or death and calculated via the Kaplan-Meier method. The log-rank test and relative risk regression were used to compare EFS distribution by age at enrollment, sex, race, NRSTS histology, prior lines of therapy, calendar year of trial, and type of radiographic response.

RESULTS: In total, 137 patients were enrolled in 13 phase 2 trials. All trials used radiographic response rate as a primary outcome, and none of the agents used were considered active on the basis of trial-specified thresholds. The estimated median EFS and 6-month EFS of the entire study cohort was 1.5 months (95% confidence interval [CI], 1.3-1.8 months) and 19.4% (95% CI, 12.7%-26%), respectively. No difference in EFS was observed by age at enrollment, sex, race, NRSTS histology subtype, prior lines of therapies, and trial initiation year. EFS significantly differed by radiographic response.

CONCLUSIONS: The EFS for children and young adults with relapsed or refractory NRSTS remains suboptimal. Established EFS can be referenced as a benchmark for future single-agent phase 2 trials incorporating potentially active novel agents in this population.

PMID:38470405 | DOI:10.1002/cncr.35276

Rom J Intern Med. 2024 Mar 12. doi: 10.2478/rjim-2024-0010. Online ahead of print.

ABSTRACT

INTRODUCTION: Accidental hypothermia (AH) presents a significant mortality risk, even in individuals with good health. Early recognition of the parameters associated with negative prognosis could save more lives.

METHODS: This was a pilot, retrospective observational study, conducted in the largest Emergency Hospital in North Eastern Romania, which included all patients with AH (defined as body temperature below 35°C), hospitalized and treated in our hospital between 2019 and 2022.

RESULTS: A total of 104 patients with AH were included in our study, 90 of whom had data collected and statistically analyzed. The clinical, biological, and therapeutic parameters associated with negative outcomes were represented by a reduced GCS score (p=0.024), diminished systolic and diastolic blood pressure (p=0.007 respectively, 0.013), decreased bicarbonate (p=0.043) and hemoglobin levels (p=0.002), the presence of coagulation disorders (p=0.007), as well as the need for administration of inotropic or vasopressor medications (p=0.04).

CONCLUSION: In this pilot, retrospective, observational study, the negative outcomes observed in patients with AH hospitalized in the largest Emergency Hospital in North-Eastern Romania were associated with several clinical, biochemical, and therapeutic factors, which are easy to identify in clinical practice. Recognizing the significance of these associated factors empowers healthcare practitioners to intervene at an early stage to save more lives.

PMID:38470364 | DOI:10.2478/rjim-2024-0010

J Phys Chem A. 2024 Mar 12. doi: 10.1021/acs.jpca.3c07416. Online ahead of print.

ABSTRACT

Recent developments in light-emitting carbon nanodots and molecular organic semiconductors have seen renewed interest in the properties of polycyclic aromatic hydrocarbons (PAHs) as a family. The networks of delocalized π electrons in sp²-hybridized carbon grant PAHs light-emissive properties right across the visible spectrum. However, the mechanistic understanding of their emission energy has been limited due to the ground state-focused methods of determination. This computational chemistry work, therefore, seeks to validate existing rules and elucidate new features and characteristics of PAHs that influence their emissions. Predictions based on (time-dependent) density functional theory account for the full 3-dimensional electronic structure of ground and excited states and reveal that twisting and near-degeneracies strongly influence emission spectra and may therefore be used to tune the color of PAHs and, hence, carbon nanodots. We particularly note that the influence of twisting goes beyond torsional destabilization of the ground-state and geometric relaxation of the excited state, with a third contribution associated with the electric transition dipole. Symmetries and peri-condensation may also have an effect, but this could not be statistically confirmed. In pursuing this goal, we demonstrate that with minimal changes to molecular size, the entire visible spectrum may be spanned by geometric modification alone; we have also provided a first estimate of emission energy for 35 molecules currently lacking published emission spectra as well as clear guidelines for when more sophisticated computational techniques are required to predict the properties of PAHs accurately.

PMID:38470339 | DOI:10.1021/acs.jpca.3c07416

Teach Learn Med. 2024 Mar 12:1-12. doi: 10.1080/10401334.2024.2326477. Online ahead of print.

ABSTRACT

Problem: A significant proportion of learning during residency takes place through informal channels. Spontaneous collaboration among medical learners significantly contributes to this informal learning and is increasingly recognized as a component of the hidden curriculum in medical education. Yet historically, a disproportionate emphasis in medical education has been placed on didactic, structured, and faculty-initiated methods, leaving an important force in medical education understudied and underutilized. We hypothesize that there is significant educational potential in studying and deploying targeted tools to facilitate collaboration among medical learners. Intervention: At our institution, neurology residents implemented the “Daily Fact Pile” (DFP), a resident-led, email-based collaboration that served as a platform to share clinical pearls in an informal, digital way. Participation was voluntary and participants were encouraged to share facts that were new to them and thought to be clinically relevant. Motivated by the positive collective experience, we conducted a retrospective examination of this phenomenon. In this context, we developed the concept of “mutual microlearning” to characterize this efficient, multidirectional exchange of information. Context: Thirty-six residents in a single neurology residency program utilized the DFP at a large university hospital in the USA between 2018 and 2019. After 21 months of spontaneous and voluntary participation, we assessed the feasibility of the DFP, its impact on the education and morale of neurology residents, and compared its mutual microlearning approach to traditional lectures. This was done through a survey of the DFP participants with a response rate of 80.7%, and analysis of the statistics of participation and interaction with the DFP. Impact: Most participants felt that the DFP was beneficial to their education and thought they often or always learned something new from reading the DFP. The impact of the DFP extended beyond education by improving interest in neurology, morale, and sense of teamwork. The DFP was feasible during neurology residency and participation was high, though participants were more likely to read facts than share them. Lessons learned: Mutual microlearning represents an opportunity to augment residents’ education, and well-designed mutual microlearning tools hold promise for complementing traditional teaching methods. We learned that efficiency, ease of use, and a supportive, non-judgmental environment are all essential to the success of such tools. Future research should delve deeper into the underlying mechanisms of mutual microlearning to establish its position within the theoretical frameworks of medical education.

PMID:38470305 | DOI:10.1080/10401334.2024.2326477

Biometrics. 2024 Jan 29;80(1):ujad039. doi: 10.1093/biomtc/ujad039.

ABSTRACT

Estimating phenotype networks is a growing field in computational biology. It deepens the understanding of disease etiology and is useful in many applications. In this study, we present a method that constructs a phenotype network by assuming a Gaussian linear structure model embedding a directed acyclic graph (DAG). We utilize genetic variants as instrumental variables and show how our method only requires access to summary statistics from a genome-wide association study (GWAS) and a reference panel of genotype data. Besides estimation, a distinct feature of the method is its summary statistics-based likelihood ratio test on directed edges. We applied our method to estimate a causal network of 29 cardiovascular-related proteins and linked the estimated network to Alzheimer’s disease (AD). A simulation study was conducted to demonstrate the effectiveness of this method. An R package sumdag implementing the proposed method, all relevant code, and a Shiny application are available.

PMID:38470257 | DOI:10.1093/biomtc/ujad039