Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients.

Background: Early research indicates that cancer patients are more vulnerable to adverse outcomes and mortality when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, the specific attributes of SARS-CoV-2 in lung Adenocarcinoma (LUAD) have not been extensively and methodically examined. Methods: We acquired 322 SARS-CoV-2 infection-related genes (CRGs) from the Human Protein Atlas database. Using an integrative machine learning approach with 10 algorithms, we developed a SARS-CoV-2 score (Cov-2S) signature across The Cancer Genome Atlas and datasets GSE72094, GSE68465, and GSE31210. Comprehensive multi-omics analysis, including assessments of genetic mutations and copy number variations, was conducted to deepen our understanding of the prognosis signature. We also analyzed the response of different Cov-2S subgroups to immunotherapy and identified targeted drugs for these subgroups, advancing personalized medicine strategies. The expression of Cov-2S genes was confirmed through qRT-PCR, with GGH emerging as a critical gene for further functional studies to elucidate its role in LUAD. Results: Out of 34 differentially expressed CRGs identified, 16 correlated with overall survival. We utilized 10 machine learning algorithms, creating 101 combinations, and selected the RFS as the optimal algorithm for constructing a Cov-2S based on the average C-index across four cohorts. This was achieved after integrating several essential clinicopathological features and 58 established signatures. We observed significant differences in biological functions and immune cell statuses within the tumor microenvironments of high and low Cov-2S groups. Notably, patients with a lower Cov-2S showed enhanced sensitivity to immunotherapy. We also identified five potential drugs targeting Cov-2S. In vitro experiments revealed a significant upregulation of GGH in LUAD, and its knockdown markedly inhibited tumor cell proliferation, migration, and invasion. Conclusion: Our research has pioneered the development of a consensus Cov-2S signature by employing an innovative approach with 10 machine learning algorithms for LUAD. Cov-2S reliably forecasts the prognosis, mirrors the tumor's local immune condition, and supports clinical decision-making in tumor therapies.

Association of Park Renovation With Park Use in New York City.

Importance: Equity-driven citywide park redesign and renovation, such as the Community Parks Initiative (CPI), has the potential to increase park use and opportunities for physical activity in underserved communities. Objective: To evaluate changes in patterns of park use following park redesign and renovation in low-income New York City (NYC) neighborhoods. Design, Setting, and Participants: The Physical Activity and Redesigned Community Spaces study was a prospective quality improvement preintervention-postintervention study design with matched control parks. Thirty-three intervention and 21 control neighborhood parks were selected based on specific criteria related to poverty rates, population growth, and population density in park neighborhoods and not having received more than $250 000 in investment in the past 2 decades. Data were collected at baseline (prerenovation) and 2 follow-up points (3 months and 1 year post renovation) between June 5 and December 4 from 2016 to 2022. Participants were individuals observed as users of study parks. Intervention: The CPI, which involved the redesign and renovation of neighborhood parks by the municipal government of New York City. Main Outcomes and Measures: Main outcomes encompassed park use and physical activity levels assessed using the well-validated System for Observing Play and Recreation in Communities. Park use was quantified by total number of park users, categorized by age group (≤20 years vs ≥21 years), sex, and physical activity level (sitting or standing vs walking or vigorous activity). Changes in outcomes between groups were compared via the generalized estimation equation. Results: A total of 28 322 park users were observed across 1458 scans. At baseline, 6343 of 10 633 users (59.7%) were 20 years or younger, 4927 of 10 632 (46.3%) were female and 5705 (53.7%) were male, and 4641 of 10 605 (43.8%) were sitting or standing. Intervention parks showed more net park users compared with control parks from baseline to the final follow-up (difference-in-difference relative rate ratio, 1.69 [95% CI, 1.22-2.35] users/scan; P = .002). The association was driven by a significant increase in adult users at intervention parks and overall decrease in all users at control parks. Park users engaging in sitting or standing at intervention parks increased (difference, 4.68 [95% CI, 1.71-7.62] users/scan; P = .002) and park users engaging in walking or vigorous physical activity at control parks decreased (difference, -7.30 [95% CI, -10.80 to -4.26] users/scan; P < .001) over time. Conclusions and Relevance: In this quality improvement study, park redesign and renovation were positively associated with park use in low-income neighborhoods. However, park renovations may need to be accompanied by other programmatic strategies to increase physical activity.

Nucleosome reorganisation in breast cancer tissues.

BACKGROUND: Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. RESULTS: We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. This analysis has detected single-nucleosome repositioning at key regulatory regions in a patient-specific manner and common cancer-specific patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with ~ 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. The tumour tissues were characterised by a 5-10 bp decrease in the average distance between nucleosomes (nucleosome repeat length, NRL), which is qualitatively similar to the differences between pluripotent and differentiated cells. This effect was correlated with gene activity, differential DNA methylation and changes in local occupancy of linker histone variants H1.4 and H1X. CONCLUSIONS: Our study offers a novel resource of high-resolution nucleosome maps in breast cancer patients and reports for the first time the effect of systematic decrease of NRL in paired tumour versus normal breast tissues from the same patient. Our findings provide a new mechanistic understanding of nucleosome repositioning in tumour tissues that can be valuable for patient diagnostics, stratification and monitoring.

Governance, policy, and health systems responses to the COVID-19 pandemic in Thailand: a qualitative study.

Background: Since 2020, Thailand has experienced four waves of COVID-19. By 31 January 2022, there were 2.4 million cumulative cases and 22,176 deaths nationwide. This study assessed the governance and policy responses adapted to different sizes of the pandemic outbreaks and other challenges. Methods: A qualitative study was applied, including literature reviews and in-depth interviews with 17 multi-sectoral actors purposively identified from those who were responsible for pandemic control and vaccine rollout. We applied deductive approaches using health systems building blocks, and inductive approaches using analysis of in-depth interview content, where key content formed sub-themes, and different sub-themes formed the themes of the study. Findings: Three themes emerged from this study. First, the large scale of COVID-19 infections, especially the Delta strain in 2021, challenged the functioning of the health system's capacity to respond to cases and maintain essential health services. The Bangkok local government insufficiently performed due to its limited capacity, ineffective multi-sectoral collaboration, and high levels of vulnerability in the population. However, adequate financing, universal health coverage, and health workforce professionalism and commitment were key enabling factors that supported the health system. Second, the population's vulnerability exacerbated infection spread, and protracted political conflicts and political interference resulted in the politicization of pandemic control measures and vaccine roll-out; all were key barriers to effective pandemic control. Third, various innovations and adaptive capacities minimized the supply-side gaps, while social capital and civil society engagement boosted community resilience. Conclusion: This study identifies key governance gaps including in public communication, managing infodemics, and inadequate coordination with Bangkok local government, and between public and private sectors on pandemic control and health service provisions. The Bangkok government had limited capacity in light of high levels of population vulnerability. These gaps were widened by political conflicts and interference. Key strengths are universal health coverage with full funding support, and health workforce commitment, innovations, and capacity to adapt interventions to the unfolding emergency. Existing social capital and civil society action increases community resilience and minimizes negative impacts on the population.

Estimating the Cost of the COVID-19 Response for Local Health Departments: Evidence From Ohio.

This study assessed the staffing allocations and associated costs incurred by Ohio local health departments (LHDs) in response to the challenges posed by the COVID-19 pandemic. Data were extracted from the annual financial reports of Ohio LHDs for 2020 and 2021, encompassing a sample of 38 LHDs in 2020 and 60 LHDs in 2021. Descriptive analysis showed that Ohio LHDs committed substantial resources to responding to the COVID-19 pandemic. Although there was considerable variability across LHDs, median staffing and compensation collectively constituted 22% of total staffing and compensation. Multivariate regression analysis found minimal associations between the examined agency and community-level variables and the differences in staffing allocations and associated costs incurred by LHDs in response to the COVID-19 pandemic. After decades of underfunding and understaffing, securing sustainable funding will be crucial to equip LHDs across the country with the necessary resources to deliver comprehensive public health services in their communities.

Understanding health system resilience in responding to COVID-19 pandemic: experiences and lessons from an evolving context of federalization in Nepal.

INTRODUCTION: The COVID-19 pandemic has tested the resilience capacities of health systems worldwide and highlighted the need to understand the concept, pathways, and elements of resilience in different country contexts. In this study, we assessed the health system response to COVID-19 in Nepal and examined the processes of policy formulation, communication, and implementation at the three tiers of government, including the dynamic interactions between tiers. Nepal was experiencing the early stages of federalization reform when COVID-19 pandemic hit the country, and clarity in roles and capacity to implement functions were the prevailing challenges, especially among the subnational governments. METHODS: We adopted a cross-sectional exploratory design, using mixed methods. We conducted a desk-based review of all policy documents introduced in response to COVID-19 from January to December 2020, and collected qualitative data through 22 key informant interviews at three tiers of government, during January-March 2021. Two municipalities were purposively selected for data collection in Lumbini province. Our analysis is based on a resilience framework that has been developed by our research project, ReBUILD for Resilience, which helps to understand pathways to health system resilience through absorption, adaptation and transformation. RESULTS: In the newly established federal structure, the existing emergency response structure and plans were utilized, which were yet to be tested in the decentralized system. The federal government effectively led the policy formulation process, but with minimal engagement of sub-national governments. Local governments could not demonstrate resilience capacities due to the novelty of the federal system and their consequent lack of experience, confusion on roles, insufficient management capacity and governance structures at local level, which was further aggravated by the limited availability of human, technical and financial resources. CONCLUSIONS: The study findings emphasize the importance of strong and flexible governance structures and strengthened capacity of subnational governments to effectively manage pandemics. The study elaborates on the key areas and pathways that contribute to the resilience capacities of health systems from the experience of Nepal. We draw out lessons that can be applied to other fragile and shock-prone settings.

The oral IRAK4 inhibitors zabedosertib and BAY1830839 suppress local and systemic immune responses in a randomized trial in healthy male volunteers.

This study evaluated and characterized the pharmacological activity of the orally administered interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors BAY1834845 (zabedosertib) and BAY1830839 in healthy male volunteers. Participants received one of either IRAK4 inhibitors or a control treatment (prednisolone 20 mg or placebo) twice daily for 7 days. Localized skin inflammation was induced by topical application of imiquimod (IMQ) cream for 3 days, starting at Day 3 of treatment. The inflammatory response was evaluated by laser speckle contrast imaging (skin perfusion) and multispectral imaging (erythema). At Day 7, participants received 1 ng/kg intravenous lipopolysaccharide (LPS). Circulating inflammatory proteins, leukocyte differentiation, acute phase proteins, and clinical parameters were evaluated before and after the systemic LPS challenge. Treatment with BAY1834845 significantly reduced the mean IMQ-induced skin perfusion response (geometric mean ratio [GMR] vs. placebo: 0.69 for BAY1834845, 0.70 for prednisolone; both p < 0.05). Treatment with BAY1834845 and BAY1830839 significantly reduced IMQ-induced erythema (GMR vs. placebo: 0.75 and 0.83, respectively, both p < 0.05; 0.86 for prednisolone, not significant). Both IRAK4 inhibitors significantly suppressed the serum TNF-α and IL-6 responses (≥80% suppression vs. placebo, p < 0.05) and inhibited C-reactive protein, procalcitonin, and IL-8 responses to intravenous LPS. This study demonstrated the pharmacological effectiveness of BAY1834845 and BAY1830839 in suppressing systemically and locally induced inflammatory responses in the same range as prednisolone, underlining the potential value of these IRAK4 inhibitors as future therapies for dermatological or other immune-mediated inflammatory diseases.

Integrating Healthy Nutrition Standards and Practices Into Food Service Contracting in a Large US County Government.

Purpose and Objectives: Although considered a promising model of practice, integrating healthy nutrition standards and practices into a large county government's contracting process with food vendors has not been widely described in empirical literature. We conducted an implementation evaluation project to address this gap. Intervention Approach: County of Los Angeles food vendors provide food or meals annually to more than 100,000 employees and millions of clients and visitors. In 2011, the County of Los Angeles Board of Supervisors adopted a policy to integrate healthy nutrition standards and practices into its requests for proposals (RFPs) and contracting process with food vendors. The policy required all contracts awarded to adhere to these new standards. Evaluation Methods: In 2011, the Los Angeles County Department of Public Health (DPH) began reviewing RFPs for food services for county departments that procured, served, or sold food. From 2011 through 2021, DPH applied a 4-pronged formative-evaluative approach to help county departments implement the Board of Supervisors policy and ensure that nutritional requirements were appropriately integrated into all RFPs for new and renewing contracts with food vendors. We focused our evaluation on understanding the process and tracking the progress of this policy intervention. Our evaluation included 13 key informant interviews, a 2-part survey, reviews of contract data, and synthesis of lessons learned. Results: Based on reviews and subsequent actions taken on more than 20 RFPs, DPH successfully assisted 7 county departments to incorporate healthy nutrition standards and practices into their food vendor contracts. Implementation of the food policy encountered several challenges, including staffing and training constraints and a limited infrastructure. An iterative approach to program improvement facilitated the process. Implications for Public Health: Although the model for integrating healthy nutrition standards and practices into a government contracting process is promising, more work is needed to make it less resource-intensive and to increase user buy-in.

When local governments' stay-at-home orders meet the white house's "opening up america again".

In the current polarized political climate, citizens frequently face conflicting directives from their local and federal government officials. For instance, on April 16th, 2020, The White House launched the "Opening up America Again" (OuAA) campaign while many U.S. counties had stay-at-home orders. We created a panel data set of U.S. counties to study the impact of U.S. counties' stay-at-home orders on community mobility before and after The White House's campaign to reopen the country. Our results suggest that before the OuAA campaign, stay-at-home orders substantially decreased the time spent in retail and recreation businesses. However, after the launch of the OuAA campaign, the time spent at retail and recreational businesses in a typical conservative county increased significantly more than in liberal counties (23% increase in a typical conservative county vs. 9% increase in a typical liberal county). We also found that in conservative counties with stay-at-home orders, time spent at retail and recreational businesses increased less than in those without stay-at-home orders. These findings illuminate that when federal and local government policies are at odds, residents decide which policies to adhere to based on the alignment between their political ideology and the government body. Our findings highlight the substantial importance of each government body in forming citizens' behaviors, offering practical implications for policy makers during natural disasters.

Association between liver enzymes and type 2 diabetes: a real-world study.

Aim: This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship. Methods: This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences. Results: A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence. Conclusion: Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.

Understanding the impact of numerical solvers on inference for differential equation models.

Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers that seem sufficiently accurate for the forward problem, i.e. for obtaining an accurate simulation, might not be sufficiently accurate for the inverse problem, i.e. for inferring the model parameters from data. We show that for both fixed step and adaptive step ODE solvers, solving the forward problem with insufficient accuracy can distort likelihood surfaces, which might become jagged, causing inference algorithms to get stuck in local 'phantom' optima. We demonstrate that biases in inference arising from numerical approximation of ODEs are potentially most severe in systems involving low noise and rapid nonlinear dynamics. We reanalyse an ODE change point model previously fit to the COVID-19 outbreak in Germany and show the effect of the step size on simulation and inference results. We then fit a more complicated rainfall run-off model to hydrological data and illustrate the importance of tuning solver tolerances to avoid distorted likelihood surfaces. Our results indicate that, when performing inference for ODE model parameters, adaptive step size solver tolerances must be set cautiously and likelihood surfaces should be inspected for characteristic signs of numerical issues.

A Framework for Evaluating Local Adaptive Capacity to Health Impacts of Climate Change: Use of Kenya's County-Level Integrated Development Plans.

Background: Health National Adaptation Plans were developed to increase the capacity of low- and middle-income countries (LMICs) to adapt to the impacts of climate change on the health sector. Climate and its health impacts vary locally, yet frameworks for evaluating the adaptive capacity of health systems on the subnational scale are lacking. In Kenya, counties prepare county integrated development plans (CIDPs), which contain information that might support evaluations of the extent to which counties are planning climate change adaptation for health. Objectives: To develop and apply a framework for evaluating CIDPs to assess the extent to which Kenya's counties are addressing the health sector's adaptive capacity to climate change. Methods: CIDPs were analyzed based on the extent to which they addressed climate change in their description of county health status, whether health is noted in their descriptions of climate change, and whether they mention plans for developing climate and health programs. Based on these and other data points, composite climate and health adaptation (CHA) scores were calculated. Associations between CHA scores and poverty rates were analyzed. Findings: CHA scores varied widely and were not associated with county-level poverty. Nearly all CIDPs noted climate change, approximately half mentioned health in the context of climate change and only 16 (34%) noted one or more specific climate-sensitive health conditions. Twelve (25%) had plans for a sub-program in both adaptive capacity and environmental health. Among the 24 counties with plans to develop climate-related programs in health programs, all specified capacity building, and 20% specified integrating health into disaster risk reduction. Conclusion: Analyses of county planning documents provide insights into the extent to which the impacts of climate change on health are being addressed at the subnational level in Kenya. This approach may support governments elsewhere in evaluating climate change adaptation for health by subnational governments.

Implementing decision aids for cardiovascular disease prevention: stakeholder interviews and case studies in Australian primary care.

BACKGROUND: Australian cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk assessment, but less than half of eligible patients have the required risk factors recorded due to fragmented implementation over the last decade. Co-designed decision aids for general practitioners (GPs) and consumers have been developed that improve knowledge barriers to guideline-recommended CVD risk assessment and management. This study used a stakeholder consultation process to identify and pilot test the feasibility of implementation strategies for these decision aids in Australian primary care. METHODS: This mixed methods study included: (1) stakeholder consultation to map existing implementation strategies (2018-20); (2) interviews with 29 Primary Health Network (PHN) staff from all Australian states and territories to identify new implementation opportunities (2021); (3) pilot testing the feasibility of low, medium, and high resource implementation strategies (2019-21). Framework Analysis was used for qualitative data and Google analytics provided decision support usage data over time. RESULTS: Informal stakeholder discussions indicated a need to partner with existing programs delivered by the Heart Foundation and PHNs. PHN interviews identified the importance of linking decision aids with GP education resources, quality improvement activities, and consumer-focused prevention programs. Participants highlighted the importance of integration with general practice processes, such as business models, workflows, medical records and clinical audit software. Specific implementation strategies were identified as feasible to pilot during COVID-19: (1) low resource: adding website links to local health area guidelines for clinicians and a Heart Foundation toolkit for primary care providers; (2) medium resource: presenting at GP education conferences and integrating the resources into audit and feedback reports; (3) high resource: auto-populate the risk assessment and decision aids from patient records via clinical audit software. CONCLUSIONS: This research identified a wide range of feasible strategies to implement decision aids for CVD risk assessment and management. The findings will inform the translation of new CVD guidelines in primary care. Future research will use economic evaluation to explore the added value of higher versus lower resource implementation strategies.

Effectiveness of Bivalent mRNA COVID-19 Vaccines in Preventing SARS-CoV-2 Infection in Children and Adolescents Aged 5 to 17 Years.

Importance: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. Objective: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. Design, Setting, and Participants: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. Exposure: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. Main Outcome and Measures: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. Results: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. Conclusion and Relevance: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

Cooking behavior among mothers of children aged 2-5 years old in Kendari, Southeast Sulawesi, Indonesia.

BACKGROUND: Cooking at home was associated with parental feeding practices. This study aimed to explore the interplay of components in cooking behavior of mothers with young children aged 2-5 years old in Kendari city of Southeast Sulawesi, Indonesia. METHODS: This qualitative study involved 33 mothers from Kendari city, which was represented by each two sub-districts in coastal and mainland areas that were randomlyselected. Six focus group discussions (FGDs) were carried out using 20-item guide questions. The guide questions were developed following the Model of Goal-Directed Behavior (MGDB) theory approach exploring the components of cooking behavior i.e., skill, intention, desire, confidence, and attitude in cooking. Data analysis was performed in the field to assist decision on data saturation, followed by data analysis at desk through multilevel coding from the verbatim transcripts using NVivo R1 software. The data was analyzed thematically using pre-determined themes according to the MGDB theory. Emerging topics on enabling factors and constraints were captured to enhance our understanding of the complexity of cooking behavior. RESULTS: The mothers' mean age was about 30 years old with a comparable representation of younger and older mothers. Most mothers were housewives and accomplished secondary school level. The mothers' intention was shown as they frequently cooked at home and allocated time for cooking. The enabling factors included their knowledge about food and nutrition, food source availability, their confidence in cooking meals and following recipes, and their motivation to keep their children healthy representing some intrinsic factors. The main constraint was the lack of skill to make snacks. The other extrinsic barriers were dependence on mobile food sellers and the availability of food kiosks that facilitated children's snack preferences. CONCLUSION: The study obtained some insights that mothers had favorable cooking intention and desire, were supported with a confidence in some basic cooking skills. However, the existing constraints that encouraged the development of unfavorable children's snacking habit were beyond the mothers' control. A cookbook specifically for snack recipes that utilizes local ingredients may assist mother in preparing more healthier options for the children.

Bayesian Vancomycin Model Selection for Therapeutic Drug Monitoring in Neonates.

BACKGROUND AND OBJECTIVE: Pharmacokinetic models can inform drug dosing of vancomycin in neonates to optimize therapy. However, the model selected needs to describe the intended population to provide appropriate dose recommendations. Our study aims to identify the population pharmacokinetic (PopPK) model(s) with the best performance to predict vancomycin exposure in neonates in our hospital. METHODS: Relevant published PopPK models for vancomycin in neonates were selected based on demographics and vancomycin dosing strategy. The predictive performance of the models was evaluated in Tucuxi using a local cohort of 69 neonates. Mean absolute error (MAE), relative bias (rBias) and relative root mean square error (rRMSE) were used to quantify the accuracy and precision of the predictive performance of each model for three different approaches: a priori, a posteriori, and Bayesian forecasting for the next course of therapy based on the previous course predictions. A PopPK model was considered clinically acceptable if rBias was between ± 20 and 95% confidence intervals included zero. RESULTS: A total of 25 PopPK models were identified and nine were considered suitable for further evaluation. The model of De Cock et al. 2014 was the only clinically acceptable model based on a priori [MAE 0.35 mg/L, rBias 0.8 % (95% confidence interval (CI) - 7.5, 9.1%), and rRMSE 8.9%], a posteriori [MAE 0.037 mg/L, rBias - 0.23% (95% CI - 1.3, 0.88%), and rRMSE 6.02%] and Bayesian forecasting for the next courses [MAE 0.89 mg/L, rBias 5.45% (95% CI - 8.2, 19.1%), and rRMSE 38.3%) approaches. CONCLUSIONS: The De Cock model was selected based on a comprehensive approach of model selection to individualize vancomycin dosing in our neonates.

Mechanical behaviors of CL-20 under an impact loading: A molecular dynamics study.

Study on the dynamic process of CL-20 crystal under impact is critical for the safe utilization of energetic materials under extreme conditions. Herein, the mechanical and structural evolution of CL-20 under the impact of a diamond ball is investigated by using molecular dynamics simulation. The considerations are given to the effect of different impact velocity, impact direction and impact angle. It is found that a high impact velocity results in a large indentation depth and force, as well as more significant energy transition and the formation of a large number of molecular fragments. Moreover, CL-20 exhibits weak anisotropy along different impact directions due to the crystalline distribution anisotropy. Furthermore, the mechanical response of CL-20 is angle-dependent, which is caused by the discrepancy in local molecular re-arrangement. These results may enhance the understanding of the mechanical behavior of CL-20 and promote its wide applications.

3D-printed guides versus computer navigation for pedicle screw placement in the surgical treatment of congenital scoliosis deformities.

BACKGROUND: To compare the safety and clinical outcomes of 3D-printed guides versus computer navigation for pedicle screw placement in the correction of congenital scoliosis deformities. METHODS: The study was a single-centre retrospective controlled study and was approved by the hospital ethics committee for the analysis all patients under the age of 18 years with at least 2 years of follow-up. Sixty-three patients who underwent surgical correction for congenital scoliosis deformities in our hospital from January 2015 to December 2020 were divided into two groups based on the decision following preoperative doctor‒patient communication. Among them, 43 patients had pedicle screws placed with 3D-printed guider plates, while the remaining 20 patients had screws inserted with the assistance of computer navigation. The perioperative period, follow-up results and imaging data were compared between the groups. RESULTS: The operation was completed successfully for patients in both groups. The 3D-printed guide-assisted screw placement technique proved to be significantly superior to the computer navigation technique in terms of operation time, screw placement time, and intraoperative blood loss (p < .05), although the former had more frequent intraoperative fluoroscopies than the latter (p < .05). The mean follow-up time was 41.4 months, and the SRS-22 scores significantly improved in both groups over time postoperatively (p < .05). The 3D-printing group had better SRS-22 scores than the navigation group 6 months after surgery and at the last follow-up (p < .05). Compared with preoperative values, the coronal Cobb angle, local kyphotic Cobb angle, C7-S1 coronal deviation (C7PL-CSVL), and sagittal deviation (SVA) were significantly improved in both groups after surgery (p < .05). CONCLUSION: Both techniques achieve the purpose of precise screw placement and proper correction of the deformities. In contrast, the 3D-printed guide-assisted screw placement technique showed advantages in terms of operation time, screw placement time, intraoperative blood loss and patient satisfaction with outcomes.

Intrauterine exposure to SARS-CoV-2 infection and early newborn brain development.

Epidemiologic studies suggest that prenatal exposures to certain viruses may influence early neurodevelopment, predisposing offspring to neuropsychiatric conditions later in life. The long-term effects of maternal COVID-19 infection in pregnancy on early brain development, however, remain largely unknown. We prospectively enrolled infants in an observational cohort study for a single-site study in the Washington, DC Metropolitan Area from June 2020 to November 2021 and compared these infants to pre-pandemic controls (studied March 2014-February 2020). The primary outcomes are measures of cortical morphometry (tissue-specific volumes), along with global and regional measures of local gyrification index, and sulcal depth. We studied 210 infants (55 infants of COVID-19 unexposed mothers, 47 infants of COVID-19-positive mothers, and 108 pre-pandemic healthy controls). We found increased cortical gray matter volume (182.45 ± 4.81 vs. 167.29 ± 2.92) and accelerated sulcal depth of the frontal lobe (5.01 ± 0.19 vs. 4.40 ± 0.13) in infants of COVID-19-positive mothers compared to controls. We found additional differences in infants of COVID-19 unexposed mothers, suggesting both maternal viral exposures, as well as non-viral stressors associated with the pandemic, may influence early development and warrant ongoing follow-up.

Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women.

PURPOSE: One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts. METHODS: Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay. RESULTS: After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF. CONCLUSIONS: ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted. Trial registration EudraCT: 2017-000317-22.