bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residential greenness, asthma, and lung function among children at high risk of allergic sensitization: a prospective cohort study
Authors: Hartley Kim , Ryan Patrick H. , Gillespie Gordon L. , Perazzo Joseph , Wright J. Michael , Rice Glenn E. , Donovan Geoffrey H. , Gernes Rebecca , Hershey Gurjit K. Khurana , LeMasters Grace , Brokamp Cole 
Published: May 2022

AbstractBackgroundWhile benefits of greenness to health have been reported, findings specific to child respiratory health are inconsistent.MethodsWe utilized a prospective birth cohort followed from birth to age 7 years (n = 617). Residential surrounding greenness was quantified via Normalized Difference Vegetation Index (NDVI) within 200, 400, and 800 m distances from geocoded home addresses at birth, age 7 years, and across childhood. Respiratory health outcomes were assessed at age 7 years, including asthma and lung function [percent predicted forced expiratory volume in the first second (%FEV1), percent predicted forced vital capacity (%FVC), and percent predicted ratio of forced expiratory volume in the first second to forced vital capacity (%FEV1/FVC)]. We assessed associations using linear and logistic regression models adjusted for community deprivation, household income, and traffic-related air pollution. We tested for effect measure modification by atopic status.ResultsWe noted evidence of positive confounding as inverse associations were attenuated upon adjustment in the multivariable models. We found evidence of effect measure modification of NDVI and asthma within 400 m at age 7 years by atopic status (p = 0.04), whereby children sensitized to common allergens were more likely to develop asthma as exposure to greenness increased (OR = 1.3, 95% CI: 0.9, 2.0) versus children not sensitized to common allergens (OR = 0.8, 95% CI: 0.5, 1.2). We found consistently positive associations between NDVI and %FEV1and %FVC which similarly evidenced positive confounding upon adjustment. In the adjusted regression models, NDVI at 7 years of age was associated with %FEV1(200 m: β = 2.1, 95% CI: 0.1, 3.3; 400 m: β = 1.6, 95% CI: 0.3, 2.9) and %FVC (200 m: β = 1.8, 95% CI: 0.7, 3.0; 400 m: β = 1.6, 95% CI: 0.3, 2.8; 800 m: β = 1.5, 95% CI: 0.1, 2.8). Adjusted results for %FEV1/FVC were non-significant except exposure at birth in the 400 m buffer (β = 0.81, 95% CI: 0.1, 1.5). We found no evidence of effect measure modification of NDVI by atopic status for objective measures of lung function.ConclusionSensitivity to allergens may modify the effect of greenness on risk for asthma in children but greenness is likely beneficial for concurrent lung function regardless of allergic status.
Key early proinflammatory signaling molecules encapsulated within circulating exosomes following traumatic injury
Authors: Walsh Sarah A. , Davis Thomas A. 
Published: May 2022

Abstract
Background
Assessment of immune status in critically ill patients is often based on serial tracking of systemic cytokine levels and clinical laboratory values. Exosomes are extracellular vesicles that can be secreted and internalized by cells to transport important cellular cargo in the regulation of numerous physiological and pathological processes. Here, we characterize the early compartmentalization profile of key proinflammatory mediators in serum exosomes in the steady state and following trauma. Adult male Sprague-Dawley rats (91 including naïve) were divided into one of four traumatic injury model groups incorporating whole-body blast, fracture, soft-tissue crush injury, tourniquet-induced ischemia, and limb amputation. Serum was collected at 1, 3, 6, and 24 h, and 3- and 7-day post-injury. Electrochemiluminescence-based immunoassays for 9 key proinflammatory mediators in whole serum, isolated serum exosomes, and exosome depleted serum were analyzed and compared between naïve and injured rats. Serum clinical chemistry analysis was performed to determine pathological changes.

Results
In naïve animals, substantial amounts of IL-1β, IL-10, and TNF-α were encapsulated, IL-6 was completely encapsulated, and CXCL1 freely circulating. One hour after blast injury alone, levels of exosome encapsulated IFN-γ, IL-10, IL-6, IL-13, IL-4, and TNF-α increased, whereas freely circulating and membrane-associated levels remained undetectable or low. Rats with the most severe polytraumatic injuries with end organ complications had the earliest rise and most pronounced concentration of IL-1β, IL-10, TNF-α, and IL-6 across all serum compartments. Moreover, CXCL1 levels increased in relation to injury severity, but remained almost entirely freely circulating at all timepoints.

Conclusion
These findings highlight that conventional ELISA-based assessments, which detect only free circulating and exosome membrane-bound mediators, underestimate the full immunoinflammatory response to trauma. Inclusion of exosome encapsulated mediators may be a better, more accurate and clinically useful early strategy to identify, diagnose, and monitor patients at highest risk for post-traumatic inflammation-associated complications.
Tumor microenvironment-responsive BSA nanocarriers for combined chemo/chemodynamic cancer therapy
Authors: Zhang Ruiyi , Liu Teng , Li Wanzhen , Ma Zhiyuan , Pei Pei , Zhang Weiwei , Yang Kai , Tao Yugui 
Published: May 2022

AbstractTumor microenvironment (TME), characterized by high glutathione (GSH), high hydrogen peroxide (H2O2) and acidic pH levels, is favorable for the growth, invasion and metastasis of cancer cells. Taking advantage of the specific characteristics of tumors, TME-responsive GCBD NPs are designed to deliver nanoscale coordination polymers (NCPs, GA-Cu) and chemotherapy drugs (doxorubicin, DOX) based on bovine serum albumin (BSA) nanocarriers into cancer cells for combined chemodynamic therapy (CDT) and chemotherapy. In an acidic environment, GCBD NPs could release approximately 90% copper ions, which can not only consume overexpressed GSH to modulate the TME but can also react with endogenous H2O2in a Fenton-like reaction to achieve the CDT effect. Meanwhile, the released DOX could enter the nucleus of tumor cells and affect their proliferation to achieve efficient chemotherapy. Both in vitro and in vivo experiments showed that GCBD NPs had good biosafety and could effectively inhibit the growth of cancer cells. GCBD NPs are promising as a biocompatible nanoplatform to exploit TME characteristics for combined chemo and chemodynamic therapy, providing a novel strategy to eradicate tumors with high efficiency and specificity.Graphical Abstract
Evaluation of the first two Frontline cohorts of the field epidemiology training program in Guinea, West Africa
Authors: Collins Doreen , Diallo Boubacar Ibrahima , Bah Mariama Boubacar , Bah Marlyatou , Standley Claire J. , Corvil Salomon , Martel Lise D. , MacDonald Pia D. M. 
Published: May 2022

Abstract
Background
The 2014–2016 Ebola virus disease outbreak in West Africa revealed weaknesses in the health systems of the three most heavily affected countries, including a shortage of public health professionals at the local level trained in surveillance and outbreak investigation. In response, the Frontline Field Epidemiology Training Program (FETP) was created by CDC in 2015 as a 3-month, accelerated training program in field epidemiology that specifically targets the district level. In Guinea, the first two FETP-Frontline cohorts were held from January to May, and from June to September 2017. Here, we report the results of a cross-sectional evaluation of these first two cohorts of FETP-Frontline in Guinea.

Methods
The evaluation was conducted in April 2018 and consisted of interviews with graduates, their supervisors, and directors of nearby health facilities, as well as direct observation of data reports and surveillance tools at health facilities. Interviews and site visits were conducted using standardized questionnaires and checklists. Qualitative data were coded under common themes and analyzed using descriptive statistics.

Results
The evaluation revealed a significant perception of improvement in all assessed skills by the graduates, as well as high levels of self-reported involvement in key activities related to data collection, analysis, and reporting. Supervisors highlighted improvements to systematic and quality case and summary reporting as key benefits of the FETP-Frontline program. At the health facility level, staff reported the training had resulted in improvements to information sharing and case notifications. Reported barriers included lack of transportation, available support personnel, and other resources. Graduates and supervisors both emphasized the importance of continued and additional training to solidify and retain skills.

Conclusions
The evaluation demonstrated a strongly positive perceived benefit of the FETP-Frontline training on the professional activities of graduates as well as the overall surveillance system. However, efforts are needed to ensure greater gender equity and to recruit more junior trainee candidates for future cohorts. Moreover, although improvements to the surveillance system were observed concurrent with the completion of the two cohorts, the evaluation was not designed to directly measure impact on surveillance or response functions. Combined with the rapid implementation of FETP-Frontline around the world, this suggests an opportunity to develop standardized evaluation toolkits, which could incorporate metrics that would directly assess the impact of equitable field epidemiology workforce development on countries’ abilities to prevent, detect, and respond to public health threats.
A systems thinking approach to understanding youth active recreation
Authors: Koorts Harriet , Salmon Paul M. , Swain Christopher T. V. , Cassar Samuel , Strickland David , Salmon Jo 
Published: May 2022

AbstractBackgroundActive recreation contributes to child and adolescent physical activity, however, factors affecting uptake are poorly understood at the systems level. The aims of this study were: (1) to use systems analysis methods to understand youth active recreation in Victoria, Australia, (ii) identify potential system leverage points to enhance active recreation, and (iii) explore stakeholder views of systems analysis methods for informing practice and policy decision-making.MethodsPhase 1: Umbrella review of systematic reviews (2013–2018), synthesising evidence for correlates, determinants and intervention evidence for promoting active recreation.Phase 2: Development of three systems models (ActorMap and two ActivMaps), depicting active recreation actors/organisations, correlates, determinants and intervention evidence.Phase 3: Development of causal loop diagrams (CLDs) and identification of leverage points based on the Action Scales Model.Phase 4: Model feedback via stakeholder interviews (n = 23; 16 organisations).ResultsFrom the literature, 93 correlates and determinants, and 49 intervention strategies were associated with child and adolescent active recreation; the majority located at a social or individual level. Ten potential system leverage points were identified in the CLDs, which differed for pre-schoolers versus children and adolescents. Only time outdoors (an event leverage point) emerged for all age groups. Changes to the built and natural environment (i.e., land use planning, urban design) as a complete domain was a key structural leverage point for influencing active recreation in children and adolescents. Subject matter experts and stakeholder interviews identified 125 actors operating across seven hierarchical active recreation system levels in Victoria. Stakeholder interviews identified 12 areas for future consideration and recommendations for practice/policy influence.ConclusionsOur findings underscore the need for dynamic models of system behaviour in active recreation, and to capture stakeholder influence as more than a transactional role in evidence generation and use. Effective responses to youth inactivity require a network of interventions that target specific leverage points across the system. Our models illustrate areas that may have the greatest system-level impact, such as changes to the built and natural environment, and they provide a tool for policy, appraisal, advocacy, and decision-making within and outside of government.
Geographical hotspots and correlates of early sexual debut among women in Ghana
Authors: Amoako Johnson Fiifi 
Published: May 2022

Abstract
Objectives
Generalisation of sexual behaviour, including early sexual initiation, does not provide comprehensive knowledge of young people’s sexual attitudes, behaviours and challenges, given the high sociocultural diversity and economic inequalities within countries. This study examines geographical hotspots of early sexual initiation, at the district level in Ghana and the factors associated with the observed spatial patterns.

Methods
Data was derived from the 2017 Ghana Maternal Health Survey, covering 21,392 women aged 15–49 years. Early sexual debut denotes first sexual intercourse before attaining the legal age of sexual consent, which in Ghana, is 16 years. The Bayesian geoadditive semiparametric regression technique was used to examine geographical hotspots and correlates of the observed spatial patterns, classified into demographic, socioeconomic and pregnancy outcome factors.

Results
The results show that 26.7% (95% CI = 26.1–27.3) of women had their first sexual intercourse before attaining the age of 16 years. Hotspots of early sexual debut was observed predominantly among districts along the mainstream of the Volta Lake, which are also reported hotspots of child trafficking, labour and slavery. Demographic, socioeconomic and pregnancy related factors were identified to be correlated with the observed spatial clustering.

Conclusion
Policies and interventions such as sexual and reproductive health education should target at-risk population, simultaneously addressing other child abuses perpetuating the practice.
Effects of acute and chronic oxidative stress on the blood–brain barrier in 2D and 3D in vitro models
Authors: Chung Tracy D. , Linville Raleigh M. , Guo Zhaobin , Ye Robert , Jha Ria , Grifno Gabrielle N. , Searson Peter C. 
Published: May 2022

AbstractOxidative stress is a shared pathology of neurodegenerative disease and brain injuries, and is derived from perturbations to normal cell processes by aging or environmental factors such as UV exposure and air pollution. As oxidative cues are often present in systemic circulation, the blood–brain barrier (BBB) plays a key role in mediating the effect of these cues on brain dysfunction. Therefore, oxidative damage and disruption of the BBB is an emergent focus of neurodegenerative disease etiology and progression. We assessed barrier dysfunction in response to chronic and acute oxidative stress in 2D and 3D in vitro models of the BBB with human iPSC-derived brain microvascular endothelial-like cells (iBMECs). We first established doses of hydrogen peroxide to induce chronic damage (modeling aging and neurodegenerative disease) and acute damage (modeling the response to traumatic brain injury) by assessing barrier function via transendothelial electrical resistance in 2D iBMEC monolayers and permeability and monolayer integrity in 3D tissue-engineered iBMEC microvessels. Following application of these chronic and acute doses in our in vitro models, we found local, discrete structural changes were the most prevalent responses (rather than global barrier loss). Additionally, we validated unique functional changes in response to oxidative stress, including dysfunctional cell turnover dynamics and immune cell adhesion that were consistent with changes in gene expression.
Overexpressing Arabidopsis thaliana ACBP6 in transgenic rapid-cycling Brassica napus confers cold tolerance
Authors: Alahakoon Aruni Y. , Tongson Eden , Meng Wei , Ye Zi-Wei , Russell Derek A. , Chye Mee-Len , Golz John F. , Taylor Paul W. J. 
Published: May 2022

Abstract
Background
Rapid-cycling Brassica napus (B. napus-RC) has potential as a rapid trait testing system for canola (B. napus) because its life cycle is completed within 2 months while canola usually takes 4 months, and it is susceptible to the same range of diseases and abiotic stress as canola. However, a rapid trait testing system for canola requires the development of an efficient transformation and tissue culture system for B. napus-RC. Furthermore, effectiveness of this system needs to be demonstrated by showing that a particular trait can be rapidly introduced into B. napus-RC plants.

Results
An in-vitro regeneration protocol was developed for B. napus-RC using 4-day-old cotyledons as the explant. High regeneration percentages, exceeding 70%, were achieved when 1-naphthaleneacetic acid (0.10 mg/L), 6-benzylaminopurine (1.0 mg/L), gibberellic acid (0.01 mg/L) and the ethylene antagonist silver nitrate (5 mg/L) were included in the regeneration medium. An average transformation efficiency of 16.4% was obtained using Agrobacterium-mediated transformation of B. napus-RC cotyledons using Agrobacterium strain GV3101 harbouring a plasmid with an NPTII (kanamycin-selectable) marker gene and the Arabidopsis thaliana cDNA encoding ACYL-COA-BINDING PROTEIN6 (AtACBP6). Transgenic B. napus-RC overexpressing AtACBP6 displayed better tolerance to freezing/frost than the wild type, with enhanced recovery from cellular membrane damage at both vegetative and flowering stages. AtACBP6-overexpressing B. napus-RC plants also exhibited lower electrolyte leakage and improved recovery following frost treatment, resulting in higher yields than the wild type. Ovules from transgenic AtACBP6 lines were better protected from frost than those of the wild type, while the developing embryos of frost-treated AtACBP6-overexpressing plants showed less freezing injury than the wild type.

Conclusions
This study demonstrates that B. napus-RC can be successfully regenerated and transformed from cotyledon explants and has the potential to be an effective trait testing platform for canola. Additionally, AtACBP6 shows potential for enhancing cold tolerance in canola however, larger scale studies will be required to further confirm this outcome.
Barriers and facilitators of implementing interventions to improve appropriate antibiotic use in low- and middle-income countries: a systematic review based on the Consolidated Framework for Implementation Research
Authors: Wu Shishi , Tannous Elias , Haldane Victoria , Ellen Moriah E. , Wei Xiaolin 
Published: May 2022

Abstract
Background
Behavior change interventions that aim to improve rational antibiotic use in prescribers and users have been widely conducted in both high- and LMICs. However, currently, no review has systematically examined challenges unique to LMICs and offered insights into the underlying contextual factors that influence these interventions. We adopted an implementation research perspective to systematically synthesize the implementation barriers and facilitators in LMICs.

Methods
We conducted literature searches in five electronic databases and identified studies that involved the implementation of behavior change interventions to improve appropriate antibiotic use in prescribers and users in LMICs and reported implementation barriers and facilitators. Behavior change interventions were defined using the behavior change wheel, and the coding and synthesis of barriers and facilitators were guided by the Consolidated Framework for Implementation Research (CFIR).

Results
We identified 52 eligible studies, with the majority targeting prescribers practicing at tertiary facilities (N=39, 75%). The most commonly reported factors influencing implementation were found in the inner setting domain of the CFIR framework, particularly related to constraints in resources and the infrastructure of the facilities where interventions were implemented. Barriers related to the external policy environment (e.g., lack of national initiatives and policies on antibiotic use), and individual characteristics of target populations (e.g., reluctance to change prescribing behaviors) were also common, as well as facilitators related to intervention characteristics (e.g., embedding interventions in routine practice) and process (e.g., stakeholder engagement). We also provided insights into the interrelationships between these factors and the underlying causes contributing to the implementation challenges in LMICs.

Conclusion
We presented a comprehensive overview of the barriers and facilitators of implementing behavior change interventions to promote rational antibiotic use in LMICs. Our findings suggest that facilitating the implementation of interventions to improve rational antibiotic use needs comprehensive efforts to address challenges at policy, organizational, and implementation levels. Specific strategies include (1) strengthening political commitment to prompt mobilization of domestic resources and formulation of a sustainable national strategy on AMR, (2) improving the infrastructure of health facilities that allow prescribers to make evidence-based clinical decisions, and (3) engaging local stakeholders to improve their buy-in and facilitate contextualizing interventions.

Trial registration
PROSPERO: CRD42021252715.
30-day mortality in patients treated for brain metastases: extracranial causes dominate
Authors: Nieder Carsten , Stanisavljevic Luka , Aanes Siv Gyda , Mannsåker Bård , Haukland Ellinor Christin 
Published: May 2022

Abstract
Background
Established prognostic models, such as the diagnosis-specific graded prognostic assessment, were not designed to specifically address very short survival. Therefore, a brain metastases-specific 30-day mortality model may be relevant. We hypothesized that in-depth evaluation of a carefully defined cohort with short survival, arbitrarily defined as a maximum of 3 months, may provide signals and insights, which facilitate the development of a 30-day mortality model.

Methods
Retrospective analysis (2011–2021) of patients treated for brain metastases with different approaches. Risk factors for 30-day mortality from radiosurgery or other primary treatment were evaluated.

Results
The cause of death was unrelated to brain metastases in 61%. Treatment-related death (grade 5 toxicity) did not occur. Completely unexpected death was not observed, e.g. accident, suicide or sudden cardiac death. Logistic regression analysis showed 9 factors associated with 30-day mortality (each assigned 3–6 points) and a point sum was calculated for each patient. The point sum ranged from 0 (no risk factors for death within 30 days present) to 30. The results can be grouped into 3 or 4 risk categories. Eighty-three percent of patients in the highest risk group (> 16 points) died within 30 days, and none survived for more than 2 months. However, many cases of 30-day mortality (more than half) occurred in intermediate risk categories.

Conclusion
Extracranial tumor progression was the prevailing cause of 30-day mortality and few, if any deaths could be considered relatively unexpected when looking at the complete oncological picture. We were able to develop a multifactorial prediction model. However, the model’s performance was not fully satisfactory and it is not routinely applicable at this point in time, because external validation is needed to confirm our hypothesis-generating findings.